Variant chr11-113214522-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_181351.5(NCAM1):c.1059+11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,592,422 control chromosomes in the GnomAD database, including 104,625 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 12815 hom., cov: 31)

Exomes 𝑓: 0.35 ( 91810 hom. )

Consequence

NCAM1
NM_181351.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.22

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCAM1	NM_181351.5 linkuse as main transcript	c.1059+11C>G		intron_variant		ENST00000316851.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAM1	ENST00000316851.12 linkuse as main transcript	c.1059+11C>G		intron_variant		5	NM_181351.5	P3	P13591-2

Frequencies

GnomAD3 genomes

AF:

0.395

AC:

59944

AN:

151810

Hom.:

12792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.545

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.376

GnomAD3 exomes

AF:

0.366

AC:

78614

AN:

214916

Hom.:

15017

AF XY:

0.363

AC XY:

42017

AN XY:

115590

show subpopulations

Gnomad AFR exome

AF:

0.549

Gnomad AMR exome

AF:

0.392

Gnomad ASJ exome

AF:

0.339

Gnomad EAS exome

AF:

0.498

Gnomad SAS exome

AF:

0.418

Gnomad FIN exome

AF:

0.218

Gnomad NFE exome

AF:

0.331

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.352

AC:

507041

AN:

1440494

Hom.:

91810

Cov.:

AF XY:

0.352

AC XY:

251350

AN XY:

714514

show subpopulations

Gnomad4 AFR exome

AF:

0.540

Gnomad4 AMR exome

AF:

0.395

Gnomad4 ASJ exome

AF:

0.336

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.406

Gnomad4 FIN exome

AF:

0.216

Gnomad4 NFE exome

AF:

0.342

Gnomad4 OTH exome

AF:

0.368

GnomAD4 genome

AF:

0.395

AC:

60013

AN:

151928

Hom.:

12815

Cov.:

AF XY:

0.389

AC XY:

28912

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.545

Gnomad4 AMR

AF:

0.379

Gnomad4 ASJ

AF:

0.356

Gnomad4 EAS

AF:

0.482

Gnomad4 SAS

AF:

0.406

Gnomad4 FIN

AF:

0.213

Gnomad4 NFE

AF:

0.333

Gnomad4 OTH

AF:

0.379

Alfa

AF:

0.266

Hom.:

923

Bravo

AF:

0.414

Asia WGS

AF:

0.475

AC:

1650

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.046

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over