rs12222469

Variant names:

• chr11-113246105-C-A
• rs12222469
• NM_181351.5:c.1826-263C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-113246105-C-A
• chr11-113246105-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_181351.5(NCAM1):​c.1826-263C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 517,088 control chromosomes in the GnomAD database, including 4,553 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 0.079 (1006 hom., cov: 33)
  • Exomes 𝑓: 0.096 (3547 hom.)
• Consequence: NCAM1 NM_181351.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAM1	NM_181351.5	c.1826-263C>A		intron_variant	Intron 14 of 19	ENST00000316851.12	NP_851996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAM1	ENST00000316851.12	c.1826-263C>A		intron_variant	Intron 14 of 19	5	NM_181351.5	ENSP00000318472.8

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 12103 AN: 152120 Hom.: 1009 Cov.: 33

Gnomad AFR AF: 0.0385

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0571

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0566

Gnomad OTH AF: 0.0840

GnomAD4 exome AF: 0.0962 AC: 35094 AN: 364850 Hom.: 3547 Cov.: 0 AF XY: 0.0977 AC XY: 18500 AN XY: 189374

Gnomad4 AFR exome AF: 0.0345

Gnomad4 AMR exome AF: 0.192

Gnomad4 ASJ exome AF: 0.0483

Gnomad4 EAS exome AF: 0.406

Gnomad4 SAS exome AF: 0.147

Gnomad4 FIN exome AF: 0.0573

Gnomad4 NFE exome AF: 0.0581

Gnomad4 OTH exome AF: 0.0829

GnomAD4 genome AF: 0.0794 AC: 12094 AN: 152238 Hom.: 1006 Cov.: 33 AF XY: 0.0859 AC XY: 6390 AN XY: 74414

Gnomad4 AFR AF: 0.0383

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0571

Gnomad4 NFE AF: 0.0565

Gnomad4 OTH AF: 0.0841

Alfa AF: 0.0219 Hom.: 13

Bravo AF: 0.0869

Asia WGS AF: 0.256 AC: 889 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs12222469; hg19: chr11-113116827;