rs143934888

Positions:

• chr19-44710483-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001039213.4(CEACAM16):​c.1268-13A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 1,611,874 control chromosomes in the GnomAD database, including 1,795 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (135 hom., cov: 33)
  • Exomes 𝑓: 0.045 (1660 hom.)
• Consequence: CEACAM16 NM_001039213.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.60

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-44710483-A-G is Benign according to our data. Variant chr19-44710483-A-G is described in ClinVar as [Benign]. Clinvar id is 226504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEACAM16	NM_001039213.4	c.1268-13A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000587331.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEACAM16	ENST00000587331.7	c.1268-13A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001039213.4	P1
CEACAM16-AS1	ENST00000662585.1	n.382-11306T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0363 AC: 5514 AN: 152092 Hom.: 135 Cov.: 33

Gnomad AFR AF: 0.00850

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0279

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.0757

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0502

Gnomad OTH AF: 0.0383

GnomAD3 exomes AF: 0.0418 AC: 10357 AN: 247654 Hom.: 303 AF XY: 0.0436 AC XY: 5854 AN XY: 134374

Gnomad AFR exome AF: 0.00725

Gnomad AMR exome AF: 0.0237

Gnomad ASJ exome AF: 0.0457

Gnomad EAS exome AF: 0.000280

Gnomad SAS exome AF: 0.0444

Gnomad FIN exome AF: 0.0793

Gnomad NFE exome AF: 0.0499

Gnomad OTH exome AF: 0.0524

GnomAD4 exome AF: 0.0455 AC: 66352 AN: 1459664 Hom.: 1660 Cov.: 31 AF XY: 0.0458 AC XY: 33218 AN XY: 726036

Gnomad4 AFR exome AF: 0.00679

Gnomad4 AMR exome AF: 0.0249

Gnomad4 ASJ exome AF: 0.0433

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0460

Gnomad4 FIN exome AF: 0.0750

Gnomad4 NFE exome AF: 0.0475

Gnomad4 OTH exome AF: 0.0464

GnomAD4 genome AF: 0.0362 AC: 5511 AN: 152210 Hom.: 135 Cov.: 33 AF XY: 0.0370 AC XY: 2752 AN XY: 74408

Gnomad4 AFR AF: 0.00847

Gnomad4 AMR AF: 0.0278

Gnomad4 ASJ AF: 0.0455

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0468

Gnomad4 FIN AF: 0.0757

Gnomad4 NFE AF: 0.0502

Gnomad4 OTH AF: 0.0379

Alfa AF: 0.0458 Hom.: 35

Bravo AF: 0.0310

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	1268-13A>G in intron 6 of CEACAM16: This variant is not expected to have clinica l significance because it has been identified in 4.7% (391/8310) of European Ame rican chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs143934888). -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	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	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.52
DANN	Benign	0.43

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: rs143934888; hg19: chr19-45213755;