chr19-44710506-A-G

Position:

• chr19-44710506-A-G

Variant summary

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

The NM_001039213.4(CEACAM16):​c.1278A>G​(p.Ter426Ter) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,613,546 control chromosomes in the GnomAD database, including 253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (17 hom., cov: 33)
  • Exomes 𝑓: 0.016 (236 hom.)
• Consequence: CEACAM16 NM_001039213.4 stop_retained
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.56

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=-0.82).
• BP6: Variant 19-44710506-A-G is Benign according to our data. Variant chr19-44710506-A-G is described in ClinVar as [Benign]. Clinvar id is 226505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.56 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.012 (1826/152270) while in subpopulation NFE AF= 0.017 (1159/68006). AF 95% confidence interval is 0.0162. There are 17 homozygotes in gnomad4. There are 864 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM16	NM_001039213.4	c.1278A>G	p.Ter426Ter	stop_retained_variant	7/7	ENST00000587331.7	NP_001034302.2
CEACAM16-AS1	NR_186815.1	n.348-11329T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM16	ENST00000587331.7	c.1278A>G	p.Ter426Ter	stop_retained_variant	7/7	1	NM_001039213.4	ENSP00000466561.1

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1828 AN: 152152 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.00352

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.00819

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0170

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.0143 AC: 3553 AN: 248868 Hom.: 35 AF XY: 0.0145 AC XY: 1952 AN XY: 135026

Gnomad AFR exome AF: 0.00239

Gnomad AMR exome AF: 0.0115

Gnomad ASJ exome AF: 0.0212

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0124

Gnomad FIN exome AF: 0.00965

Gnomad NFE exome AF: 0.0194

Gnomad OTH exome AF: 0.0212

GnomAD4 exome AF: 0.0164 AC: 23922 AN: 1461276 Hom.: 236 Cov.: 31 AF XY: 0.0162 AC XY: 11764 AN XY: 726960

Gnomad4 AFR exome AF: 0.00269

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.0210

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0120

Gnomad4 FIN exome AF: 0.00995

Gnomad4 NFE exome AF: 0.0181

Gnomad4 OTH exome AF: 0.0162

GnomAD4 genome AF: 0.0120 AC: 1826 AN: 152270 Hom.: 17 Cov.: 33 AF XY: 0.0116 AC XY: 864 AN XY: 74442

Gnomad4 AFR AF: 0.00351

Gnomad4 AMR AF: 0.0165

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.00819

Gnomad4 NFE AF: 0.0170

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0135 Hom.: 10

Bravo AF: 0.0120

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0187

EpiControl AF: 0.0186

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 31, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 03, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2015	p.X426X in exon 7 of CEACAM16: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 2.0% (1379/67626) o f European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs146757817). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 30, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs146757817; hg19: chr19-45213778;