rs894189

chr19-44703425-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001039213.4(CEACAM16):c.114G>A(p.Thr38=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 1,613,668 control chromosomes in the GnomAD database, including 6,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1622 hom., cov: 32)
  • Exomes 𝑓: 0.065 (4416 hom.)
• Consequence: CEACAM16 NM_001039213.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.62

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

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-44703425-G-A is Benign according to our data. Variant chr19-44703425-G-A is described in ClinVar as [Benign]. Clinvar id is 226502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.62 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEACAM16	NM_001039213.4	c.114G>A	p.Thr38=	synonymous_variant	3/7	ENST00000587331.7
CEACAM16	XM_017026795.2	c.114G>A	p.Thr38=	synonymous_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEACAM16	ENST00000587331.7	c.114G>A	p.Thr38=	synonymous_variant	3/7	1	NM_001039213.4	P1
CEACAM16-AS1	ENST00000662585.1	n.382-4248C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17918 AN: 152092 Hom.: 1612 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.0501

Gnomad SAS AF: 0.0972

Gnomad FIN AF: 0.0547

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0516

Gnomad OTH AF: 0.111

GnomAD3 exomes AF: 0.0913 AC: 22708 AN: 248662 Hom.: 1637 AF XY: 0.0855 AC XY: 11550 AN XY: 135034

Gnomad AFR exome AF: 0.252

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.0607

Gnomad EAS exome AF: 0.0430

Gnomad SAS exome AF: 0.0903

Gnomad FIN exome AF: 0.0604

Gnomad NFE exome AF: 0.0548

Gnomad OTH exome AF: 0.0860

GnomAD4 exome AF: 0.0653 AC: 95370 AN: 1461458 Hom.: 4416 Cov.: 33 AF XY: 0.0647 AC XY: 47012 AN XY: 727032

Gnomad4 AFR exome AF: 0.251

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.0597

Gnomad4 EAS exome AF: 0.0484

Gnomad4 SAS exome AF: 0.0897

Gnomad4 FIN exome AF: 0.0605

Gnomad4 NFE exome AF: 0.0530

Gnomad4 OTH exome AF: 0.0763

GnomAD4 genome AF: 0.118 AC: 17944 AN: 152210 Hom.: 1622 Cov.: 32 AF XY: 0.118 AC XY: 8794 AN XY: 74438

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.0628

Gnomad4 EAS AF: 0.0498

Gnomad4 SAS AF: 0.0964

Gnomad4 FIN AF: 0.0547

Gnomad4 NFE AF: 0.0516

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0753 Hom.: 871

Bravo AF: 0.134

Asia WGS AF: 0.0860 AC: 297 AN: 3478

EpiCase AF: 0.0544

EpiControl AF: 0.0574

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Thr38Thr in exon 3 of CEACAM16: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 22.9% (951/4144) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs894189). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 03, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.016
Dann	Benign	0.67

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

Other links and lift over

dbSNP: rs894189; hg19: chr19-45206695; COSMIC: COSV101312677;