11-113214522-C-G

Variant names:

• chr11-113214522-C-G
• rs686050
• NM_181351.5:c.1059+11C>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.1059+11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,592,422 control chromosomes in the GnomAD database, including 104,625 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 0.40 (12815 hom., cov: 31)
  • Exomes 𝑓: 0.35 (91810 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: 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 = 0.539 is higher than 0.05.

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>G		intron	N/A	NP_851996.2	P13591-2
	NCAM1	NM_001400624.1		c.1059+11C>G		intron	N/A	NP_001387553.1
	NCAM1	NM_001400620.1		c.1059+11C>G		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>G		intron	N/A	ENSP00000318472.8	P13591-2
	NCAM1	ENST00000529356.5	TSL:1	c.1059+11C>G		intron	N/A	ENSP00000482205.1	P13591-6
	NCAM1	ENST00000619839.4	TSL:5	c.1059+11C>G		intron	N/A	ENSP00000480132.1	A0A087WWD4

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59944 AN: 151810 Hom.: 12792 Cov.: 31

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.376

GnomAD2 exomes AF: 0.366 AC: 78614 AN: 214916 AF XY: 0.363

Gnomad AFR exome AF: 0.549

Gnomad AMR exome AF: 0.392

Gnomad ASJ exome AF: 0.339

Gnomad EAS exome AF: 0.498

Gnomad FIN exome AF: 0.218

Gnomad NFE exome AF: 0.331

Gnomad OTH exome AF: 0.354

GnomAD4 exome AF: 0.352 AC: 507041 AN: 1440494 Hom.: 91810 Cov.: 35 AF XY: 0.352 AC XY: 251350 AN XY: 714514

African (AFR) AF: 0.540 AC: 17853 AN: 33036

American (AMR) AF: 0.395 AC: 16196 AN: 41034

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 8633 AN: 25706

East Asian (EAS) AF: 0.500 AC: 19418 AN: 38830

South Asian (SAS) AF: 0.406 AC: 33679 AN: 82980

European-Finnish (FIN) AF: 0.216 AC: 11313 AN: 52366

Middle Eastern (MID) AF: 0.321 AC: 1840 AN: 5740

European-Non Finnish (NFE) AF: 0.342 AC: 376125 AN: 1101104

Other (OTH) AF: 0.368 AC: 21984 AN: 59698

GnomAD4 genome AF: 0.395 AC: 60013 AN: 151928 Hom.: 12815 Cov.: 31 AF XY: 0.389 AC XY: 28912 AN XY: 74294

African (AFR) AF: 0.545 AC: 22540 AN: 41380

American (AMR) AF: 0.379 AC: 5798 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1237 AN: 3470

East Asian (EAS) AF: 0.482 AC: 2476 AN: 5142

South Asian (SAS) AF: 0.406 AC: 1955 AN: 4816

European-Finnish (FIN) AF: 0.213 AC: 2253 AN: 10578

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22622 AN: 67946

Other (OTH) AF: 0.379 AC: 800 AN: 2110

Alfa AF: 0.266 Hom.: 923

Bravo AF: 0.414

Asia WGS AF: 0.475 AC: 1650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.046
DANN	Benign	0.43
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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; COSMIC: COSV57516951;