NM_181351.5:c.53-16390G>A

Variant names:

• chr11-113185989-G-A
• rs2196456
• NM_181351.5:c.53-16390G>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.53-16390G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 152,252 control chromosomes in the GnomAD database, including 53,879 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 (53879 hom., cov: 33)
• Consequence: NCAM1 NM_181351.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.777
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAM1	NM_181351.5	c.53-16390G>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.53-16390G>A		intron_variant	Intron 1 of 19	5	NM_181351.5	ENSP00000318472.8

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127452 AN: 152134 Hom.: 53820 Cov.: 33

Gnomad AFR AF: 0.941

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.832

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

GnomAD4 genome AF: 0.838 AC: 127570 AN: 152252 Hom.: 53879 Cov.: 33 AF XY: 0.839 AC XY: 62417 AN XY: 74434

African (AFR) AF: 0.941 AC: 39112 AN: 41564

American (AMR) AF: 0.866 AC: 13244 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2630 AN: 3470

East Asian (EAS) AF: 0.863 AC: 4467 AN: 5176

South Asian (SAS) AF: 0.825 AC: 3982 AN: 4824

European-Finnish (FIN) AF: 0.782 AC: 8287 AN: 10598

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53101 AN: 68008

Other (OTH) AF: 0.830 AC: 1754 AN: 2112

Alfa AF: 0.816 Hom.: 6333

Bravo AF: 0.850

Asia WGS AF: 0.807 AC: 2810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.80
PhyloP100		0.78
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: rs2196456; hg19: chr11-113056711;