rs199779296

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001039213.4(CEACAM16):c.738G>A(p.Thr246=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00407 in 1,613,772 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 20 hom. )

Consequence

CEACAM16
NM_001039213.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -4.44

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 19-44705666-G-A is Benign according to our data. Variant chr19-44705666-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 500433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-44705666-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-4.44 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00281 (428/152270) while in subpopulation NFE AF= 0.00472 (321/68004). AF 95% confidence interval is 0.00429. There are 1 homozygotes in gnomad4. There are 210 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 20 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM16	NM_001039213.4 linkuse as main transcript	c.738G>A	p.Thr246=	synonymous_variant	5/7	ENST00000587331.7	NP_001034302.2
CEACAM16	XM_017026795.2 linkuse as main transcript	c.738G>A	p.Thr246=	synonymous_variant	4/5		XP_016882284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM16	ENST00000587331.7 linkuse as main transcript	c.738G>A	p.Thr246=	synonymous_variant	5/7	1	NM_001039213.4	ENSP00000466561	P1
CEACAM16-AS1	ENST00000662585.1 linkuse as main transcript	n.382-6489C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00281

AC:

428

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00452

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00472

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00350

AC:

870

AN:

248464

Hom.:

AF XY:

0.00349

AC XY:

471

AN XY:

134810

show subpopulations

Gnomad AFR exome

AF:

0.000453

Gnomad AMR exome

AF:

0.000464

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00483

Gnomad NFE exome

AF:

0.00639

Gnomad OTH exome

AF:

0.00398

GnomAD4 exome

AF:

0.00421

AC:

6148

AN:

1461502

Hom.:

Cov.:

AF XY:

0.00409

AC XY:

2970

AN XY:

727014

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00567

Gnomad4 NFE exome

AF:

0.00507

Gnomad4 OTH exome

AF:

0.00270

GnomAD4 genome

AF:

0.00281

AC:

428

AN:

152270

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

210

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000987

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00452

Gnomad4 NFE

AF:

0.00472

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00386

Hom.:

Bravo

AF:

0.00220

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00376

EpiControl

AF:

0.00451

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

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	Nov 01, 2022	CEACAM16: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 30, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 05, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Mar 17, 2022	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 27, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Thr246Thr in exon 5 of CEACAM16: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 0.4% (32/8468) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS). -

CEACAM16-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 24, 2020

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

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.68

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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