Variant chr11-113207325-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_181351.5(NCAM1):c.693C>T(p.Val231=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,614,026 control chromosomes in the GnomAD database, including 204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0098 ( 8 hom., cov: 32)

Exomes 𝑓: 0.015 ( 196 hom. )

Consequence

NCAM1
NM_181351.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.117

Variant links:

Genes affected

NCAM1 (HGNC:7656): (neural cell adhesion molecule 1) This gene encodes a cell adhesion protein which is a member of the immunoglobulin superfamily. The encoded protein is involved in cell-to-cell interactions as well as cell-matrix interactions during development and differentiation. The encoded protein plays a role in the development of the nervous system by regulating neurogenesis, neurite outgrowth, and cell migration. This protein is also involved in the expansion of T lymphocytes, B lymphocytes and natural killer (NK) cells which play an important role in immune surveillance. This protein plays a role in signal transduction by interacting with fibroblast growth factor receptors, N-cadherin and other components of the extracellular matrix and by triggering signalling cascades involving FYN-focal adhesion kinase (FAK), mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K). One prominent isoform of this gene, cell surface molecule CD56, plays a role in several myeloproliferative disorders such as acute myeloid leukemia and differential expression of this gene is associated with differential disease progression. For example, increased expression of CD56 is correlated with lower survival in acute myeloid leukemia patients whereas increased severity of COVID-19 is correlated with decreased abundance of CD56-expressing NK cells in peripheral blood. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Aug 2020]

NCAM1 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=-0.32).

BP6

Variant 11-113207325-C-T is Benign according to our data. Variant chr11-113207325-C-T is described in ClinVar as [Benign]. Clinvar id is 770406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.117 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00975 (1486/152360) while in subpopulation NFE AF= 0.0159 (1083/68032). AF 95% confidence interval is 0.0151. There are 8 homozygotes in gnomad4. There are 700 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1486 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCAM1	NM_181351.5 linkuse as main transcript	c.693C>T	p.Val231=	synonymous_variant	6/20	ENST00000316851.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAM1	ENST00000316851.12 linkuse as main transcript	c.693C>T	p.Val231=	synonymous_variant	6/20	5	NM_181351.5	P3	P13591-2

Frequencies

GnomAD3 genomes

AF:

0.00975

AC:

1485

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00273

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00704

Gnomad FIN

AF:

0.00367

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0159

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00979

AC:

2441

AN:

249266

Hom.:

AF XY:

0.0102

AC XY:

1373

AN XY:

135232

show subpopulations

Gnomad AFR exome

AF:

0.00316

Gnomad AMR exome

AF:

0.00744

Gnomad ASJ exome

AF:

0.00735

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00533

Gnomad FIN exome

AF:

0.00450

Gnomad NFE exome

AF:

0.0152

Gnomad OTH exome

AF:

0.0140

GnomAD4 exome

AF:

0.0149

AC:

21710

AN:

1461666

Hom.:

196

Cov.:

AF XY:

0.0145

AC XY:

10561

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.00254

Gnomad4 AMR exome

AF:

0.00780

Gnomad4 ASJ exome

AF:

0.00635

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00581

Gnomad4 FIN exome

AF:

0.00442

Gnomad4 NFE exome

AF:

0.0176

Gnomad4 OTH exome

AF:

0.0132

GnomAD4 genome

AF:

0.00975

AC:

1486

AN:

152360

Hom.:

Cov.:

AF XY:

0.00939

AC XY:

700

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00272

Gnomad4 AMR

AF:

0.0101

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00725

Gnomad4 FIN

AF:

0.00367

Gnomad4 NFE

AF:

0.0159

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.0102

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0166

EpiControl

AF:

0.0161

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

8.2

DANN

Benign

0.69

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

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