19-44703362-T-C

Position:

• chr19-44703362-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The ENST00000587331.7(CEACAM16):​c.51T>C​(p.Asn17Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,609,440 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (112 hom.)
• Consequence: CEACAM16 ENST00000587331.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.32

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:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-44703362-T-C is Benign according to our data. Variant chr19-44703362-T-C is described in ClinVar as [Benign]. Clinvar id is 196306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-44703362-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-2.32 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00114 (173/152222) while in subpopulation SAS AF= 0.0347 (167/4812). AF 95% confidence interval is 0.0304. There are 5 homozygotes in gnomad4. There are 130 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM16	NM_001039213.4	c.51T>C	p.Asn17Asn	synonymous_variant	3/7	ENST00000587331.7	NP_001034302.2
CEACAM16	XM_017026795.2	c.51T>C	p.Asn17Asn	synonymous_variant	2/5		XP_016882284.1
CEACAM16-AS1	NR_186815.1	n.348-4185A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM16	ENST00000587331.7	c.51T>C	p.Asn17Asn	synonymous_variant	3/7	1	NM_001039213.4	ENSP00000466561.1

Frequencies

GnomAD3 genomes AF: 0.00113 AC: 172 AN: 152104 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0345

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00545 AC: 1342 AN: 246300 Hom.: 45 AF XY: 0.00742 AC XY: 993 AN XY: 133868

Gnomad AFR exome AF: 0.0000656

Gnomad AMR exome AF: 0.0000581

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad SAS exome AF: 0.0429

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000542

Gnomad OTH exome AF: 0.00350

GnomAD4 exome AF: 0.00254 AC: 3699 AN: 1457218 Hom.: 112 Cov.: 32 AF XY: 0.00374 AC XY: 2711 AN XY: 723966

Gnomad4 AFR exome AF: 0.0000599

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0405

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000271

Gnomad4 OTH exome AF: 0.00263

GnomAD4 genome AF: 0.00114 AC: 173 AN: 152222 Hom.: 5 Cov.: 32 AF XY: 0.00175 AC XY: 130 AN XY: 74456

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0347

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000246 Hom.: 0

Bravo AF: 0.000359

Asia WGS AF: 0.0200 AC: 68 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	Eurofins Ntd Llc (ga)	Jan 16, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 07, 2016	p.Asn17Asn in exon 3 of CEACAM16: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 699/15188 (4.6%) of South Asian chromosomes including 24 homozygotes by the Exome Aggregation Co nsortium (ExAC, http://exac.broadinstitute.org; dbSNP rs202230938). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 29, 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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.67
DANN	Benign	0.21

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: rs202230938; hg19: chr19-45206632;