chr11-113233274-T-G

Variant names:

• chr11-113233274-T-G
• rs584427
• NM_181351.5:c.1650T>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_181351.5(NCAM1):​c.1650T>G​(p.Val550Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,612,636 control chromosomes in the GnomAD database, including 248,768 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 0.62 (30656 hom., cov: 31)
  • Exomes 𝑓: 0.54 (218112 hom.)
• Consequence: NCAM1 NM_181351.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 30 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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=1.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAM1	NM_181351.5	c.1650T>G	p.Val550Val	synonymous_variant	Exon 13 of 20	ENST00000316851.12	NP_851996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAM1	ENST00000316851.12	c.1650T>G	p.Val550Val	synonymous_variant	Exon 13 of 20	5	NM_181351.5	ENSP00000318472.8

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93313 AN: 151744 Hom.: 30597 Cov.: 31

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.581

GnomAD2 exomes AF: 0.549 AC: 135900 AN: 247606 AF XY: 0.541

Gnomad AFR exome AF: 0.861

Gnomad AMR exome AF: 0.491

Gnomad ASJ exome AF: 0.492

Gnomad EAS exome AF: 0.735

Gnomad FIN exome AF: 0.464

Gnomad NFE exome AF: 0.521

Gnomad OTH exome AF: 0.541

GnomAD4 exome AF: 0.542 AC: 791942 AN: 1460774 Hom.: 218112 Cov.: 54 AF XY: 0.539 AC XY: 391528 AN XY: 726582

African (AFR) AF: 0.864 AC: 28915 AN: 33474

American (AMR) AF: 0.502 AC: 22369 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 12776 AN: 26114

East Asian (EAS) AF: 0.714 AC: 28315 AN: 39680

South Asian (SAS) AF: 0.520 AC: 44790 AN: 86130

European-Finnish (FIN) AF: 0.462 AC: 24627 AN: 53362

Middle Eastern (MID) AF: 0.513 AC: 2955 AN: 5760

European-Non Finnish (NFE) AF: 0.534 AC: 593429 AN: 1111346

Other (OTH) AF: 0.560 AC: 33766 AN: 60348

GnomAD4 genome AF: 0.615 AC: 93421 AN: 151862 Hom.: 30656 Cov.: 31 AF XY: 0.609 AC XY: 45151 AN XY: 74198

African (AFR) AF: 0.855 AC: 35427 AN: 41446

American (AMR) AF: 0.526 AC: 8031 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1750 AN: 3468

East Asian (EAS) AF: 0.726 AC: 3732 AN: 5140

South Asian (SAS) AF: 0.530 AC: 2541 AN: 4798

European-Finnish (FIN) AF: 0.460 AC: 4832 AN: 10506

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35295 AN: 67930

Other (OTH) AF: 0.587 AC: 1238 AN: 2110

Alfa AF: 0.552 Hom.: 99655

Bravo AF: 0.631

Asia WGS AF: 0.655 AC: 2278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.70
PhyloP100		1.0
PromoterAI		-0.016	Neutral
Mutation Taster		=96/4	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: rs584427; hg19: chr11-113103996; COSMIC: COSV57516520; COSMIC: COSV57516520;