rs12418058

Variant names:

• chr11-113037332-T-C
• rs12418058
• NM_181351.5:c.52+75668T>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+75668T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0418 in 152,284 control chromosomes in the GnomAD database, including 451 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 0.042 (451 hom., cov: 32)
• Consequence: NCAM1 NM_181351.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.138 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.52+75668T>C		intron	N/A	NP_851996.2	P13591-2
	NCAM1	NM_001400624.1		c.52+75668T>C		intron	N/A	NP_001387553.1
	NCAM1	NM_001400620.1		c.52+75668T>C		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.52+75668T>C		intron	N/A	ENSP00000318472.8	P13591-2
	NCAM1	ENST00000529356.5	TSL:1	c.52+75668T>C		intron	N/A	ENSP00000482205.1	P13591-6
	NCAM1	ENST00000619839.4	TSL:5	c.52+75668T>C		intron	N/A	ENSP00000480132.1	A0A087WWD4

Frequencies

GnomAD3 genomes AF: 0.0419 AC: 6374 AN: 152166 Hom.: 451 Cov.: 32

Gnomad AFR AF: 0.0289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00390

Gnomad OTH AF: 0.0287

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

GnomAD4 genome AF: 0.0418 AC: 6372 AN: 152284 Hom.: 451 Cov.: 32 AF XY: 0.0521 AC XY: 3883 AN XY: 74466

African (AFR) AF: 0.0289 AC: 1202 AN: 41568

American (AMR) AF: 0.143 AC: 2188 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3468

East Asian (EAS) AF: 0.141 AC: 732 AN: 5186

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4820

European-Finnish (FIN) AF: 0.172 AC: 1824 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00390 AC: 265 AN: 68022

Other (OTH) AF: 0.0279 AC: 59 AN: 2112

Alfa AF: 0.0126 Hom.: 53

Bravo AF: 0.0407

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.64
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: rs12418058; hg19: chr11-112908054;