11-113243136-C-G

Variant names:

• chr11-113243136-C-G
• rs620291
• NM_181351.5:c.1826-3232C>G

Variant summary

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

The NM_181351.5(NCAM1):​c.1826-3232C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 152,266 control chromosomes in the GnomAD database, including 53,343 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 0.84 (53343 hom., cov: 34)
• Consequence: NCAM1 NM_181351.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181351.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAM1	NM_181351.5	MANE Select	c.1826-3232C>G		intron	N/A	NP_851996.2
	NCAM1	NM_001400624.1		c.1825+7972C>G		intron	N/A	NP_001387553.1
	NCAM1	NM_001400620.1		c.1810+6821C>G		intron	N/A	NP_001387549.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAM1	ENST00000316851.12	TSL:5 MANE Select	c.1826-3232C>G		intron	N/A	ENSP00000318472.8
	NCAM1	ENST00000533073.5	TSL:1	c.322+7972C>G		intron	N/A	ENSP00000486406.1
	NCAM1	ENST00000619839.4	TSL:5	c.1904-3232C>G		intron	N/A	ENSP00000480132.1

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127266 AN: 152148 Hom.: 53309 Cov.: 34

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.846

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

GnomAD4 genome AF: 0.836 AC: 127354 AN: 152266 Hom.: 53343 Cov.: 34 AF XY: 0.834 AC XY: 62110 AN XY: 74464

African (AFR) AF: 0.838 AC: 34809 AN: 41550

American (AMR) AF: 0.824 AC: 12610 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 3027 AN: 3470

East Asian (EAS) AF: 0.843 AC: 4355 AN: 5166

South Asian (SAS) AF: 0.908 AC: 4387 AN: 4832

European-Finnish (FIN) AF: 0.794 AC: 8418 AN: 10604

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56818 AN: 68024

Other (OTH) AF: 0.844 AC: 1782 AN: 2112

Alfa AF: 0.830 Hom.: 6133

Bravo AF: 0.839

Asia WGS AF: 0.849 AC: 2952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.031
DANN	Benign	0.49
PhyloP100		-1.4
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: rs620291; hg19: chr11-113113858;