rs12279261

Variant names:

• chr11-113235733-A-G
• rs12279261
• NM_181351.5:c.1825+569A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-113235733-A-G
• chr11-113235733-A-T

Variant summary

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

The NM_181351.5(NCAM1):​c.1825+569A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,120 control chromosomes in the GnomAD database, including 4,891 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 0.22 (4891 hom., cov: 33)
• Consequence: NCAM1 NM_181351.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAM1	NM_181351.5	c.1825+569A>G		intron_variant	Intron 14 of 19	ENST00000316851.12	NP_851996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAM1	ENST00000316851.12	c.1825+569A>G		intron_variant	Intron 14 of 19	5	NM_181351.5	ENSP00000318472.8

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34054 AN: 152002 Hom.: 4876 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0700

Gnomad SAS AF: 0.0503

Gnomad FIN AF: 0.0906

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.224 AC: 34107 AN: 152120 Hom.: 4891 Cov.: 33 AF XY: 0.217 AC XY: 16116 AN XY: 74380

African (AFR) AF: 0.404 AC: 16742 AN: 41464

American (AMR) AF: 0.192 AC: 2934 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 574 AN: 3468

East Asian (EAS) AF: 0.0702 AC: 363 AN: 5174

South Asian (SAS) AF: 0.0499 AC: 241 AN: 4828

European-Finnish (FIN) AF: 0.0906 AC: 960 AN: 10598

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11515 AN: 67990

Other (OTH) AF: 0.233 AC: 493 AN: 2114

Alfa AF: 0.191 Hom.: 9844

Bravo AF: 0.242

Asia WGS AF: 0.0790 AC: 273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.44
PhyloP100		-0.19
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: rs12279261; hg19: chr11-113106455;