rs1369816

Variant names:

• chr11-113121979-A-C
• rs1369816
• NM_181351.5:c.53-80400A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-113121979-A-C
• chr11-113121979-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.53-80400A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,096 control chromosomes in the GnomAD database, including 45,632 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 0.77 (45632 hom., cov: 32)
• Consequence: NCAM1 NM_181351.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAM1	NM_181351.5	c.53-80400A>C		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.53-80400A>C		intron_variant	Intron 1 of 19	5	NM_181351.5	ENSP00000318472.8

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117480 AN: 151976 Hom.: 45606 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.793

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

GnomAD4 genome AF: 0.773 AC: 117555 AN: 152096 Hom.: 45632 Cov.: 32 AF XY: 0.769 AC XY: 57174 AN XY: 74344

African (AFR) AF: 0.739 AC: 30642 AN: 41482

American (AMR) AF: 0.825 AC: 12611 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2791 AN: 3472

East Asian (EAS) AF: 0.521 AC: 2687 AN: 5158

South Asian (SAS) AF: 0.846 AC: 4075 AN: 4814

European-Finnish (FIN) AF: 0.736 AC: 7769 AN: 10562

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54256 AN: 68000

Other (OTH) AF: 0.789 AC: 1669 AN: 2114

Alfa AF: 0.768 Hom.: 5840

Bravo AF: 0.778

Asia WGS AF: 0.733 AC: 2545 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.3
DANN	Benign	0.74
PhyloP100		-0.51
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: rs1369816; hg19: chr11-112992701;