rs186687142

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001039213.4(CEACAM16):c.95G>T(p.Ser32Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,613,786 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. S32S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0018 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 6 hom. )

Consequence

CEACAM16
NM_001039213.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0190

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069971085).

BP6

Variant 19-44703406-G-T is Benign according to our data. Variant chr19-44703406-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00182 (277/152320) while in subpopulation AMR AF = 0.00954 (146/15300). AF 95% confidence interval is 0.00828. There are 2 homozygotes in GnomAd4. There are 132 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM16	NM_001039213.4 link	c.95G>T	p.Ser32Ile	missense_variant	Exon 3 of 7	ENST00000587331.7	NP_001034302.2	Q2WEN9
CEACAM16	XM_017026795.2 link	c.95G>T	p.Ser32Ile	missense_variant	Exon 2 of 5		XP_016882284.1
CEACAM16-AS1	NR_186815.1 link	n.348-4229C>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM16	ENST00000587331.7 link	c.95G>T	p.Ser32Ile	missense_variant	Exon 3 of 7	1	NM_001039213.4	ENSP00000466561.1		Q2WEN9

Frequencies

GnomAD3 genomes

AF:

0.00183

AC:

279

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00969

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00144

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00196

AC:

488

AN:

248360

AF XY:

0.00168

show subpopulations

Gnomad AFR exome

AF:

0.000195

Gnomad AMR exome

AF:

0.00785

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000836

Gnomad NFE exome

AF:

0.00165

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00159

AC:

2327

AN:

1461466

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

1116

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33480

American (AMR)

AF:

0.00899

AC:

402

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.000191

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.000921

AC:

AN:

53194

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00158

AC:

1757

AN:

1111864

Other (OTH)

AF:

0.00174

AC:

105

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

131

262

393

524

655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.00182

AC:

277

AN:

152320

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

132

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41584

American (AMR)

AF:

0.00954

AC:

146

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000942

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00144

AC:

AN:

68012

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00154

Hom.:

Bravo

AF:

0.00265

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00132

AC:

ExAC

AF:

0.00190

AC:

230

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.00172

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

May 30, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

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, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CEACAM16: BP4, BS2 -

not specified

Benign:1

May 14, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Ser32Ile in exon 3 of CEACAM16: This variant is not expected to have clinical significance because it has been identified in 0.9% (109/11536) of Latino chromo somes including 3 homozygotes by the Exome Aggregation Consortium (ExAC, http:// exac.broadinstitute.org; dbSNP rs186687142). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.1

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.051

T;T

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.57

.;T

MetaRNN

Benign

0.0070

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.1

L;L

PhyloP100

0.019

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.9

.;N

REVEL

Benign

0.042

Sift

Uncertain

0.0060

.;D

Sift4G

Benign

0.069

T;T

Vest4

0.20

MVP

0.47

MPC

0.17

ClinPred

0.010

GERP RS

1.9

Varity_R

0.085

gMVP

0.50

Mutation Taster

=100/0

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