dbSNP rs646558: NCAM1:c.1825+21C>A (chr11-113235185-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_181351.5(NCAM1):c.1825+21C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,613,474 control chromosomes in the GnomAD database, including 44,872 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 0.28 ( 7443 hom., cov: 33)

Exomes 𝑓: 0.22 ( 37429 hom. )

Consequence

NCAM1
NM_181351.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0490

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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAM1	NM_181351.5 link	c.1825+21C>A		intron_variant	Intron 14 of 19	ENST00000316851.12	NP_851996.2	P13591-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAM1	ENST00000316851.12 link	c.1825+21C>A		intron_variant	Intron 14 of 19	5	NM_181351.5	ENSP00000318472.8		P13591-2

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43179

AN:

152046

Hom.:

7420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.489

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.255

GnomAD3 exomes

AF:

0.217

AC:

53744

AN:

248066

Hom.:

6763

AF XY:

0.206

AC XY:

27793

AN XY:

134762

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.230

Gnomad ASJ exome

AF:

0.144

Gnomad EAS exome

AF:

0.238

Gnomad SAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.215

GnomAD4 exome

AF:

0.219

AC:

319586

AN:

1461310

Hom.:

37429

Cov.:

AF XY:

0.214

AC XY:

155524

AN XY:

726908

show subpopulations

Gnomad4 AFR exome

AF:

0.508

Gnomad4 AMR exome

AF:

0.237

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.219

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.193

Gnomad4 NFE exome

AF:

0.220

Gnomad4 OTH exome

AF:

0.221

GnomAD4 genome

AF:

0.284

AC:

43254

AN:

152164

Hom.:

7443

Cov.:

AF XY:

0.278

AC XY:

20665

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.489

Gnomad4 AMR

AF:

0.234

Gnomad4 ASJ

AF:

0.146

Gnomad4 EAS

AF:

0.243

Gnomad4 SAS

AF:

0.123

Gnomad4 FIN

AF:

0.195

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.259

Alfa

AF:

0.224

Hom.:

3570

Bravo

AF:

0.301

Asia WGS

AF:

0.210

AC:

734

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.5

DANN

Benign

0.66

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over