11-113271850-C-T

Position:

• chr11-113271850-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_181351.5(NCAM1):​c.2430C>T​(p.Asn810=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,570,946 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0023 (12 hom.)
• Consequence: NCAM1 NM_181351.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.532

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]

NCAM1-AS1 (HGNC:48675): (NCAM1 antisense RNA1)

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 11-113271850-C-T is Benign according to our data. Variant chr11-113271850-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642376.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.532 with no splicing effect.
• BS2: High AC in GnomAd4 at 300 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCAM1	NM_181351.5	c.2430C>T	p.Asn810=	synonymous_variant	19/20	ENST00000316851.12	NP_851996.2
NCAM1-AS1	NR_034101.1	n.279-1329G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCAM1	ENST00000316851.12	c.2430C>T	p.Asn810=	synonymous_variant	19/20	5	NM_181351.5	ENSP00000318472	P3
NCAM1-AS1	ENST00000662696.1	n.343-1329G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00197 AC: 300 AN: 152050 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00294

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00208 AC: 380 AN: 182278 Hom.: 2 AF XY: 0.00220 AC XY: 214 AN XY: 97198

Gnomad AFR exome AF: 0.000299

Gnomad AMR exome AF: 0.00115

Gnomad ASJ exome AF: 0.0101

Gnomad EAS exome AF: 0.000236

Gnomad SAS exome AF: 0.00122

Gnomad FIN exome AF: 0.000683

Gnomad NFE exome AF: 0.00257

Gnomad OTH exome AF: 0.00267

GnomAD4 exome AF: 0.00235 AC: 3330 AN: 1418778 Hom.: 12 Cov.: 30 AF XY: 0.00234 AC XY: 1643 AN XY: 701524

Gnomad4 AFR exome AF: 0.000495

Gnomad4 AMR exome AF: 0.00136

Gnomad4 ASJ exome AF: 0.0113

Gnomad4 EAS exome AF: 0.000135

Gnomad4 SAS exome AF: 0.00115

Gnomad4 FIN exome AF: 0.000872

Gnomad4 NFE exome AF: 0.00243

Gnomad4 OTH exome AF: 0.00265

GnomAD4 genome AF: 0.00197 AC: 300 AN: 152168 Hom.: 0 Cov.: 30 AF XY: 0.00175 AC XY: 130 AN XY: 74414

Gnomad4 AFR AF: 0.000434

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00294

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00303 Hom.: 3

Bravo AF: 0.00182

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

NCAM1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	7.0
DANN	Benign	0.88

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: rs200459186; hg19: chr11-113142572;