rs1943620

Variant names:

• chr11-113194571-G-A
• rs1943620
• NM_181351.5:c.53-7808G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181351.5(NCAM1):​c.53-7808G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,068 control chromosomes in the GnomAD database, including 14,894 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 0.42 (14894 hom., cov: 32)
• Consequence: NCAM1 NM_181351.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 12 publications found

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]

ENSG00000310174 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAM1	NM_181351.5	c.53-7808G>A		intron_variant	Intron 1 of 19	ENST00000316851.12	NP_851996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAM1	ENST00000316851.12	c.53-7808G>A		intron_variant	Intron 1 of 19	5	NM_181351.5	ENSP00000318472.8

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63618 AN: 151950 Hom.: 14871 Cov.: 32

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.398

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.419 AC: 63689 AN: 152068 Hom.: 14894 Cov.: 32 AF XY: 0.413 AC XY: 30676 AN XY: 74336

African (AFR) AF: 0.623 AC: 25844 AN: 41498

American (AMR) AF: 0.436 AC: 6651 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1247 AN: 3468

East Asian (EAS) AF: 0.448 AC: 2316 AN: 5166

South Asian (SAS) AF: 0.400 AC: 1925 AN: 4818

European-Finnish (FIN) AF: 0.210 AC: 2227 AN: 10588

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22303 AN: 67952

Other (OTH) AF: 0.400 AC: 844 AN: 2108

Alfa AF: 0.362 Hom.: 42710

Bravo AF: 0.447

Asia WGS AF: 0.467 AC: 1622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.038
DANN	Benign	0.38
PhyloP100		-1.2
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: rs1943620; hg19: chr11-113065293;