chr19-44703406-G-T

Position:

chr19-44703406-G-T

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). 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

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:):

CEACAM16-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 226511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-44703406-G-T is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM16	NM_001039213.4 linkuse as main transcript	c.95G>T	p.Ser32Ile	missense_variant	3/7	ENST00000587331.7	NP_001034302.2	Q2WEN9
CEACAM16	XM_017026795.2 linkuse as main transcript	c.95G>T	p.Ser32Ile	missense_variant	2/5		XP_016882284.1
CEACAM16-AS1	NR_186815.1 linkuse as main transcript	n.348-4229C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM16	ENST00000587331.7 linkuse as main transcript	c.95G>T	p.Ser32Ile	missense_variant	3/7	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

GnomAD3 exomes

AF:

0.00196

AC:

488

AN:

248360

Hom.:

AF XY:

0.00168

AC XY:

226

AN XY:

134848

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 SAS 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

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00899

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000921

Gnomad4 NFE exome

AF:

0.00158

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00182

AC:

277

AN:

152320

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

132

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00954

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00144

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00133

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 30, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2023	CEACAM16: BP4, BS2 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

May 14, 2015

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over