Variant 19-44708135-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001039213.4(CEACAM16):c.1215T>C(p.Thr405Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 1,606,178 control chromosomes in the GnomAD database, including 591,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 59993 hom., cov: 33)

Exomes 𝑓: 0.85 ( 531874 hom. )

Consequence

CEACAM16
NM_001039213.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.92

Variant links:

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 links:

CEACAM16-AS1 (HGNC:):

CEACAM16-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 19-44708135-T-C is Benign according to our data. Variant chr19-44708135-T-C is described in ClinVar as [Benign]. Clinvar id is 769228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM16	NM_001039213.4 linkuse as main transcript	c.1215T>C	p.Thr405Thr	synonymous_variant	6/7	ENST00000587331.7	NP_001034302.2	Q2WEN9
CEACAM16	XM_017026795.2 linkuse as main transcript	c.1215T>C	p.Thr405Thr	synonymous_variant	5/5		XP_016882284.1
CEACAM16-AS1	NR_186815.1 linkuse as main transcript	n.348-8958A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM16	ENST00000587331.7 linkuse as main transcript	c.1215T>C	p.Thr405Thr	synonymous_variant	6/7	1	NM_001039213.4	ENSP00000466561.1		Q2WEN9

Frequencies

GnomAD3 genomes

AF:

0.885

AC:

134654

AN:

152154

Hom.:

59930

Cov.:

show subpopulations

Gnomad AFR

AF:

0.968

Gnomad AMI

AF:

0.819

Gnomad AMR

AF:

0.929

Gnomad ASJ

AF:

0.831

Gnomad EAS

AF:

0.757

Gnomad SAS

AF:

0.901

Gnomad FIN

AF:

0.774

Gnomad MID

AF:

0.943

Gnomad NFE

AF:

0.854

Gnomad OTH

AF:

0.892

GnomAD4 exome

AF:

0.855

AC:

1242633

AN:

1453906

Hom.:

531874

Cov.:

AF XY:

0.855

AC XY:

617749

AN XY:

722278

show subpopulations

Gnomad4 AFR exome

AF:

0.973

Gnomad4 AMR exome

AF:

0.952

Gnomad4 ASJ exome

AF:

0.840

Gnomad4 EAS exome

AF:

0.782

Gnomad4 SAS exome

AF:

0.894

Gnomad4 FIN exome

AF:

0.785

Gnomad4 NFE exome

AF:

0.849

Gnomad4 OTH exome

AF:

0.865

GnomAD4 genome

AF:

0.885

AC:

134775

AN:

152272

Hom.:

59993

Cov.:

AF XY:

0.883

AC XY:

65718

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.968

Gnomad4 AMR

AF:

0.930

Gnomad4 ASJ

AF:

0.831

Gnomad4 EAS

AF:

0.757

Gnomad4 SAS

AF:

0.900

Gnomad4 FIN

AF:

0.774

Gnomad4 NFE

AF:

0.854

Gnomad4 OTH

AF:

0.894

Alfa

AF:

0.859

Hom.:

48562

Bravo

AF:

0.898

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 30, 2023

The p.Thr405Thr variant in CEACAM16 is classified as benign because it has been identified in 96.8% (40107/41446) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org). Additionally it does not alter an amino acid residue, is not located within the splice consensus site, and computational splice prediction tools do not predict an impact on splicing. ACMG/AMP Criteria applied: BA1, BP4, BP7. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.12

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over