19-44710483-A-G

Variant names:

• chr19-44710483-A-G
• rs143934888
• NM_001039213.4:c.1268-13A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001039213.4(CEACAM16):​c.1268-13A>G variant causes a 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 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.60
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039213.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM16	NM_001039213.4	MANE Select	c.1268-13A>G		intron	N/A	NP_001034302.2
	CEACAM16-AS1	NR_186815.1		n.348-11306T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM16	ENST00000587331.7	TSL:1 MANE Select	c.1268-13A>G		intron	N/A	ENSP00000466561.1
	CEACAM16	ENST00000405314.2	TSL:5	c.1268-13A>G		intron	N/A	ENSP00000385576.1
	CEACAM16-AS1	ENST00000590796.1	TSL:5	n.314+5467T>C		intron	N/A

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

GnomAD2 exomes AF: 0.0418 AC: 10357 AN: 247654 AF XY: 0.0436

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 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

African (AFR) AF: 0.00679 AC: 227 AN: 33444

American (AMR) AF: 0.0249 AC: 1111 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.0433 AC: 1129 AN: 26064

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39580

South Asian (SAS) AF: 0.0460 AC: 3960 AN: 86084

European-Finnish (FIN) AF: 0.0750 AC: 4001 AN: 53356

Middle Eastern (MID) AF: 0.0687 AC: 395 AN: 5748

European-Non Finnish (NFE) AF: 0.0475 AC: 52730 AN: 1110518

Other (OTH) AF: 0.0464 AC: 2794 AN: 60260

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

African (AFR) AF: 0.00847 AC: 352 AN: 41534

American (AMR) AF: 0.0278 AC: 426 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0455 AC: 158 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.0468 AC: 226 AN: 4824

European-Finnish (FIN) AF: 0.0757 AC: 802 AN: 10600

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0502 AC: 3415 AN: 67972

Other (OTH) AF: 0.0379 AC: 80 AN: 2112

Alfa AF: 0.0456 Hom.: 120

Bravo AF: 0.0310

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.52
DANN	Benign	0.43
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs143934888; hg19: chr19-45213755; COSMIC: COSV107509113;