11-113214522-C-T

Variant names:

• chr11-113214522-C-T
• rs686050
• NM_181351.5:c.1059+11C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181351.5(NCAM1):​c.1059+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,593,136 control chromosomes in the GnomAD database, including 1 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 0.000013 (1 hom., cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NCAM1 NM_181351.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.22
• Publications: 16 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAM1	NM_181351.5	MANE Select	c.1059+11C>T		intron	N/A	NP_851996.2	P13591-2
	NCAM1	NM_001400624.1		c.1059+11C>T		intron	N/A	NP_001387553.1
	NCAM1	NM_001400620.1		c.1059+11C>T		intron	N/A	NP_001387549.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAM1	ENST00000316851.12	TSL:5 MANE Select	c.1059+11C>T		intron	N/A	ENSP00000318472.8	P13591-2
	NCAM1	ENST00000529356.5	TSL:1	c.1059+11C>T		intron	N/A	ENSP00000482205.1	P13591-6
	NCAM1	ENST00000619839.4	TSL:5	c.1059+11C>T		intron	N/A	ENSP00000480132.1	A0A087WWD4

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151880 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441256 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 714914

African (AFR) AF: 0.00 AC: 0 AN: 33056

American (AMR) AF: 0.00 AC: 0 AN: 41090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25712

East Asian (EAS) AF: 0.00 AC: 0 AN: 38858

South Asian (SAS) AF: 0.00 AC: 0 AN: 83022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101678

Other (OTH) AF: 0.0000167 AC: 1 AN: 59718

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151880 Hom.: 1 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 74202

African (AFR) AF: 0.0000484 AC: 2 AN: 41300

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 923

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.044
DANN	Benign	0.68
PhyloP100		-3.2

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: rs686050; hg19: chr11-113085244;