rs200297676

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001039213.4(CEACAM16):c.508G>A(p.Ala170Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,593,496 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 8 hom. )

Consequence

CEACAM16
NM_001039213.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: -0.281

Publications

2 publications found

Variant links:

Genes affected

CEACAM16 (HGNC:31948): (CEA cell adhesion molecule 16, tectorial membrane component) The protein encoded by this gene is a secreted glycoprotein that in mouse interacts with tectorial membrane proteins in the inner ear. The encoded adhesion protein is found in cochlear outer hair cells and appears to be important for proper hearing over an extended frequency range. Defects in this gene likely are a cause of non-syndromic autosomal dominant hearing loss. [provided by RefSeq, May 2012]

CEACAM16 links:

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

CEACAM16-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007554978).

BP6

Variant 19-44704143-G-A is Benign according to our data. Variant chr19-44704143-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 226508.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00114 (174/152380) while in subpopulation SAS AF = 0.00228 (11/4834). AF 95% confidence interval is 0.00164. There are 0 homozygotes in GnomAd4. There are 85 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 8 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CEACAM16	NM_001039213.4 link	c.508G>A	p.Ala170Thr	missense_variant	Exon 4 of 7	ENST00000587331.7	NP_001034302.2
CEACAM16	XM_017026795.2 link	c.508G>A	p.Ala170Thr	missense_variant	Exon 3 of 5		XP_016882284.1
CEACAM16-AS1	NR_186815.1 link	n.348-4966C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM16	ENST00000587331.7 link	c.508G>A	p.Ala170Thr	missense_variant	Exon 4 of 7	1	NM_001039213.4	ENSP00000466561.1

Frequencies

GnomAD3 genomes

AF:

0.00115

AC:

175

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000719

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00227

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00191

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.00173

AC:

364

AN:

210060

AF XY:

0.00198

show subpopulations

Gnomad AFR exome

AF:

0.000262

Gnomad AMR exome

AF:

0.000548

Gnomad ASJ exome

AF:

0.000108

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000160

Gnomad NFE exome

AF:

0.00239

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00193

AC:

2786

AN:

1441116

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

1431

AN XY:

715416

show subpopulations

African (AFR)

AF:

0.000335

AC:

AN:

32862

American (AMR)

AF:

0.000640

AC:

AN:

42196

Ashkenazi Jewish (ASJ)

AF:

0.000233

AC:

AN:

25740

East Asian (EAS)

AF:

0.00

AC:

AN:

38164

South Asian (SAS)

AF:

0.00385

AC:

320

AN:

83170

European-Finnish (FIN)

AF:

0.000275

AC:

AN:

50892

Middle Eastern (MID)

AF:

0.00460

AC:

AN:

5222

European-Non Finnish (NFE)

AF:

0.00207

AC:

2289

AN:

1103392

Other (OTH)

AF:

0.00160

AC:

AN:

59478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

190

380

570

760

950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00114

AC:

174

AN:

152380

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74528

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41580

American (AMR)

AF:

0.000718

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00228

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00191

AC:

130

AN:

68042

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.00123

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000773

AC:

ESP6500EA

AF:

0.00232

AC:

ExAC

AF:

0.00167

AC:

200

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:4

Jul 13, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CEACAM16: BP4 -

Nov 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Uncertain:1

Jun 09, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.508G>A (p.A170T) alteration is located in exon 4 (coding exon 3) of the CEACAM16 gene. This alteration results from a G to A substitution at nucleotide position 508, causing the alanine (A) at amino acid position 170 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not specified

Benign:1

Apr 30, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Ala170Thr in exon 4 of CEACAM16: This variant is not expected to have clinical significance because it has been identified in 0.48% (47/9884) South Asian chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs200297676), and because of a lack of conservation across species, inc luding mammals. Of note, squirrel, dolphin, killer whale, and armadillo have a t hreonine (Thr) at this position despite high nearby amino acid conservation. In addition, computational prediction tools do not suggest a high likelihood of imp act to the protein. -

CEACAM16-related disorder

Benign:1

Oct 17, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.2

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0096

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.61

.;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.0076

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.18

N;N

PhyloP100

-0.28

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.64

.;N

REVEL

Benign

0.031

Sift

Uncertain

0.026

.;D

Sift4G

Benign

0.29

T;T

Vest4

0.11

MVP

0.040

MPC

0.14

ClinPred

0.0036

GERP RS

-3.3

Varity_R

0.10

gMVP

0.18

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over