chr11-113009875-G-C

Variant names:

• chr11-113009875-G-C
• rs1884
• NM_181351.5:c.52+48211G>C

Variant summary

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

The NM_181351.5(NCAM1):​c.52+48211G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,998 control chromosomes in the GnomAD database, including 5,750 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 0.26 (5750 hom., cov: 31)
• Consequence: NCAM1 NM_181351.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAM1	NM_181351.5	MANE Select	c.52+48211G>C		intron	N/A	NP_851996.2
	NCAM1	NM_001400624.1		c.52+48211G>C		intron	N/A	NP_001387553.1
	NCAM1	NM_001400620.1		c.52+48211G>C		intron	N/A	NP_001387549.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAM1	ENST00000316851.12	TSL:5 MANE Select	c.52+48211G>C		intron	N/A	ENSP00000318472.8
	NCAM1	ENST00000529356.5	TSL:1	c.52+48211G>C		intron	N/A	ENSP00000482205.1
	NCAM1	ENST00000619839.4	TSL:5	c.52+48211G>C		intron	N/A	ENSP00000480132.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39929 AN: 151880 Hom.: 5743 Cov.: 31

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.263 AC: 39957 AN: 151998 Hom.: 5750 Cov.: 31 AF XY: 0.269 AC XY: 20015 AN XY: 74306

African (AFR) AF: 0.181 AC: 7516 AN: 41462

American (AMR) AF: 0.261 AC: 3986 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3470

East Asian (EAS) AF: 0.529 AC: 2726 AN: 5156

South Asian (SAS) AF: 0.509 AC: 2453 AN: 4822

European-Finnish (FIN) AF: 0.314 AC: 3313 AN: 10558

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18069 AN: 67944

Other (OTH) AF: 0.280 AC: 590 AN: 2106

Alfa AF: 0.260 Hom.: 691

Bravo AF: 0.252

Asia WGS AF: 0.468 AC: 1628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.38
PhyloP100		0.055
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: rs1884; hg19: chr11-112880597;