rs635596

chr11-113242793-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181351.5(NCAM1):c.1826-3575G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,611,638 control chromosomes in the GnomAD database, including 562,701 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 0.81 (49954 hom., cov: 32)
  • Exomes 𝑓: 0.84 (512747 hom.)
• Consequence: NCAM1 NM_181351.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.61).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCAM1	NM_181351.5	c.1826-3575G>A		intron_variant		ENST00000316851.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAM1	ENST00000316851.12	c.1826-3575G>A		intron_variant		5	NM_181351.5	P3

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122961 AN: 151962 Hom.: 49925 Cov.: 32

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.824

GnomAD3 exomes AF: 0.838 AC: 208835 AN: 249234 Hom.: 87877 AF XY: 0.844 AC XY: 114073 AN XY: 135224

Gnomad AFR exome AF: 0.737

Gnomad AMR exome AF: 0.849

Gnomad ASJ exome AF: 0.872

Gnomad EAS exome AF: 0.832

Gnomad SAS exome AF: 0.910

Gnomad FIN exome AF: 0.799

Gnomad NFE exome AF: 0.835

Gnomad OTH exome AF: 0.831

GnomAD4 exome AF: 0.837 AC: 1222377 AN: 1459558 Hom.: 512747 Cov.: 42 AF XY: 0.840 AC XY: 609969 AN XY: 726190

Gnomad4 AFR exome AF: 0.742

Gnomad4 AMR exome AF: 0.843

Gnomad4 ASJ exome AF: 0.870

Gnomad4 EAS exome AF: 0.853

Gnomad4 SAS exome AF: 0.912

Gnomad4 FIN exome AF: 0.802

Gnomad4 NFE exome AF: 0.834

Gnomad4 OTH exome AF: 0.839

GnomAD4 genome AF: 0.809 AC: 123042 AN: 152080 Hom.: 49954 Cov.: 32 AF XY: 0.807 AC XY: 59991 AN XY: 74338

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.812

Gnomad4 ASJ AF: 0.872

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.904

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.834

Gnomad4 OTH AF: 0.822

Alfa AF: 0.825 Hom.: 10689

Bravo AF: 0.807

Asia WGS AF: 0.843 AC: 2929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	3.4
Dann	Benign	0.70

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: rs635596; hg19: chr11-113113515;