rs677642

Variant names:

• chr11-113219458-G-C
• rs677642
• NM_181351.5:c.1060-1838G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-113219458-G-C
• chr11-113219458-G-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.1060-1838G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 152,138 control chromosomes in the GnomAD database, including 12,383 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 0.39 (12383 hom., cov: 33)
• Consequence: NCAM1 NM_181351.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.282
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAM1	NM_181351.5	c.1060-1838G>C		intron_variant	Intron 8 of 19	ENST00000316851.12	NP_851996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAM1	ENST00000316851.12	c.1060-1838G>C		intron_variant	Intron 8 of 19	5	NM_181351.5	ENSP00000318472.8

Frequencies

GnomAD3 genomes AF: 0.388 AC: 59017 AN: 152020 Hom.: 12359 Cov.: 33

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.388 AC: 59083 AN: 152138 Hom.: 12383 Cov.: 33 AF XY: 0.382 AC XY: 28411 AN XY: 74388

African (AFR) AF: 0.537 AC: 22299 AN: 41508

American (AMR) AF: 0.379 AC: 5804 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1234 AN: 3462

East Asian (EAS) AF: 0.413 AC: 2138 AN: 5176

South Asian (SAS) AF: 0.394 AC: 1898 AN: 4820

European-Finnish (FIN) AF: 0.209 AC: 2216 AN: 10580

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22377 AN: 67976

Other (OTH) AF: 0.374 AC: 791 AN: 2116

Alfa AF: 0.340 Hom.: 1116

Bravo AF: 0.406

Asia WGS AF: 0.449 AC: 1561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.43
PhyloP100		-0.28
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: rs677642; hg19: chr11-113090180;