rs10426475

Positions:

• chr19-44707847-C-T

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.941-14C>T 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 0.0418 in 1,514,672 control chromosomes in the GnomAD database, including 2,023 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (393 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1630 hom.)
• Consequence: CEACAM16 NM_001039213.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.207

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=-0.82).
• BP6: Variant 19-44707847-C-T is Benign according to our data. Variant chr19-44707847-C-T is described in ClinVar as [Benign]. Clinvar id is 226510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM16	NM_001039213.4	c.941-14C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000587331.7	NP_001034302.2
CEACAM16	XM_017026795.2	c.941-14C>T		splice_polypyrimidine_tract_variant, intron_variant			XP_016882284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM16	ENST00000587331.7	c.941-14C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001039213.4	ENSP00000466561	P1
CEACAM16-AS1	ENST00000662585.1	n.382-8670G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9057 AN: 152106 Hom.: 391 Cov.: 32

Gnomad AFR AF: 0.0865

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.0512

Gnomad SAS AF: 0.0811

Gnomad FIN AF: 0.0451

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0311

Gnomad OTH AF: 0.0630

GnomAD3 exomes AF: 0.0636 AC: 10971 AN: 172482 Hom.: 607 AF XY: 0.0598 AC XY: 5513 AN XY: 92222

Gnomad AFR exome AF: 0.0891

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.0263

Gnomad EAS exome AF: 0.0419

Gnomad SAS exome AF: 0.0726

Gnomad FIN exome AF: 0.0516

Gnomad NFE exome AF: 0.0312

Gnomad OTH exome AF: 0.0510

GnomAD4 exome AF: 0.0399 AC: 54319 AN: 1362448 Hom.: 1630 Cov.: 29 AF XY: 0.0402 AC XY: 26763 AN XY: 665002

Gnomad4 AFR exome AF: 0.0877

Gnomad4 AMR exome AF: 0.170

Gnomad4 ASJ exome AF: 0.0272

Gnomad4 EAS exome AF: 0.0486

Gnomad4 SAS exome AF: 0.0745

Gnomad4 FIN exome AF: 0.0496

Gnomad4 NFE exome AF: 0.0310

Gnomad4 OTH exome AF: 0.0449

GnomAD4 genome AF: 0.0595 AC: 9061 AN: 152224 Hom.: 393 Cov.: 32 AF XY: 0.0622 AC XY: 4626 AN XY: 74426

Gnomad4 AFR AF: 0.0863

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0308

Gnomad4 EAS AF: 0.0510

Gnomad4 SAS AF: 0.0805

Gnomad4 FIN AF: 0.0451

Gnomad4 NFE AF: 0.0311

Gnomad4 OTH AF: 0.0619

Alfa AF: 0.0398 Hom.: 68

Bravo AF: 0.0680

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 01, 2018	- -

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	941-14C>T in intron 5 of CEACAM16: This variant is not expected to have clinical significance because it has been identified in 8.2% (354/4340) of African Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs10426475). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.78
DANN	Benign	0.40

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: rs10426475; hg19: chr19-45211119;