NM_181351.5:c.53-82247A>G

Variant names:

• chr11-113120132-A-G
• rs11214505
• NM_181351.5:c.53-82247A>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.53-82247A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 152,314 control chromosomes in the GnomAD database, including 269 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 0.053 (269 hom., cov: 32)
• Consequence: NCAM1 NM_181351.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAM1	NM_181351.5	c.53-82247A>G		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.53-82247A>G		intron_variant	Intron 1 of 19	5	NM_181351.5	ENSP00000318472.8

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 8004 AN: 152196 Hom.: 270 Cov.: 32

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0780

Gnomad FIN AF: 0.0426

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0814

Gnomad OTH AF: 0.0555

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

GnomAD4 genome AF: 0.0525 AC: 7999 AN: 152314 Hom.: 269 Cov.: 32 AF XY: 0.0509 AC XY: 3788 AN XY: 74484

African (AFR) AF: 0.0142 AC: 591 AN: 41580

American (AMR) AF: 0.0382 AC: 585 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0571 AC: 198 AN: 3468

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5176

South Asian (SAS) AF: 0.0781 AC: 377 AN: 4830

European-Finnish (FIN) AF: 0.0426 AC: 453 AN: 10624

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0814 AC: 5534 AN: 68008

Other (OTH) AF: 0.0549 AC: 116 AN: 2112

Alfa AF: 0.0760 Hom.: 284

Bravo AF: 0.0506

Asia WGS AF: 0.0300 AC: 106 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	7.5
DANN	Benign	0.57
PhyloP100		0.37
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: rs11214505; hg19: chr11-112990854;