NM_181351.5:c.53-87131A>G

Variant names:

• chr11-113115248-A-G
• rs892954
• NM_181351.5:c.53-87131A>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.53-87131A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 152,074 control chromosomes in the GnomAD database, including 48,329 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 0.80 (48329 hom., cov: 31)
• Consequence: NCAM1 NM_181351.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 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.53-87131A>G		intron	N/A	NP_851996.2
	NCAM1	NM_001400624.1		c.53-87131A>G		intron	N/A	NP_001387553.1
	NCAM1	NM_001400620.1		c.53-87131A>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.53-87131A>G		intron	N/A	ENSP00000318472.8
	NCAM1	ENST00000529356.5	TSL:1	c.53-87131A>G		intron	N/A	ENSP00000482205.1
	NCAM1	ENST00000619839.4	TSL:5	c.53-87131A>G		intron	N/A	ENSP00000480132.1

Frequencies

GnomAD3 genomes AF: 0.796 AC: 120886 AN: 151956 Hom.: 48282 Cov.: 31

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.788

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

GnomAD4 genome AF: 0.796 AC: 120988 AN: 152074 Hom.: 48329 Cov.: 31 AF XY: 0.795 AC XY: 59120 AN XY: 74338

African (AFR) AF: 0.875 AC: 36318 AN: 41496

American (AMR) AF: 0.779 AC: 11896 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2592 AN: 3470

East Asian (EAS) AF: 0.737 AC: 3797 AN: 5154

South Asian (SAS) AF: 0.691 AC: 3326 AN: 4812

European-Finnish (FIN) AF: 0.804 AC: 8495 AN: 10566

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51976 AN: 67990

Other (OTH) AF: 0.787 AC: 1659 AN: 2108

Alfa AF: 0.790 Hom.: 8315

Bravo AF: 0.798

Asia WGS AF: 0.720 AC: 2504 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.40
PhyloP100		-0.91
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: rs892954; hg19: chr11-112985970;