rs61902539

Positions:

• chr11-113242430-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_181351.5(NCAM1):​c.1826-3938G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0354 in 152,104 control chromosomes in the GnomAD database, including 103 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 0.035 (103 hom., cov: 33)
• Consequence: NCAM1 NM_181351.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.358

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0354 (5377/152104) while in subpopulation AFR AF= 0.0465 (1928/41496). AF 95% confidence interval is 0.0447. There are 103 homozygotes in gnomad4. There are 2552 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5377 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCAM1	NM_181351.5	c.1826-3938G>T		intron_variant		ENST00000316851.12	NP_851996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCAM1	ENST00000316851.12	c.1826-3938G>T		intron_variant		5	NM_181351.5	ENSP00000318472	P3

Frequencies

GnomAD3 genomes AF: 0.0353 AC: 5370 AN: 151986 Hom.: 103 Cov.: 33

Gnomad AFR AF: 0.0464

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.0374

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.00983

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0382

Gnomad OTH AF: 0.0417

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

GnomAD4 genome AF: 0.0354 AC: 5377 AN: 152104 Hom.: 103 Cov.: 33 AF XY: 0.0343 AC XY: 2552 AN XY: 74366

Gnomad4 AFR AF: 0.0465

Gnomad4 AMR AF: 0.0285

Gnomad4 ASJ AF: 0.0374

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.00983

Gnomad4 NFE AF: 0.0382

Gnomad4 OTH AF: 0.0413

Alfa AF: 0.0340 Hom.: 12

Bravo AF: 0.0377

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.89

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

Other links and lift over

dbSNP: rs61902539; hg19: chr11-113113152;