rs2072546

chr7-108232372-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001037132.4(NRCAM):c.381C>T(p.Asn127=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,609,834 control chromosomes in the GnomAD database, including 25,042 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 0.14 (2362 hom., cov: 32)
  • Exomes 𝑓: 0.15 (22680 hom.)
• Consequence: NRCAM NM_001037132.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.651

Genes affected

NRCAM (HGNC:7994): (neuronal cell adhesion molecule) Cell adhesion molecules (CAMs) are members of the immunoglobulin superfamily. This gene encodes a neuronal cell adhesion molecule with multiple immunoglobulin-like C2-type domains and fibronectin type-III domains. This ankyrin-binding protein is involved in neuron-neuron adhesion and promotes directional signaling during axonal cone growth. This gene is also expressed in non-neural tissues and may play a general role in cell-cell communication via signaling from its intracellular domain to the actin cytoskeleton during directional cell migration. Allelic variants of this gene have been associated with autism and addiction vulnerability. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=-0.651 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRCAM	NM_001037132.4	c.381C>T	p.Asn127=	synonymous_variant	7/33	ENST00000379028.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRCAM	ENST00000379028.8	c.381C>T	p.Asn127=	synonymous_variant	7/33	5	NM_001037132.4	P1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20714 AN: 151990 Hom.: 2361 Cov.: 32

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.137

GnomAD3 exomes AF: 0.205 AC: 50713 AN: 246956 Hom.: 7790 AF XY: 0.202 AC XY: 26924 AN XY: 133474

Gnomad AFR exome AF: 0.0259

Gnomad AMR exome AF: 0.364

Gnomad ASJ exome AF: 0.110

Gnomad EAS exome AF: 0.578

Gnomad SAS exome AF: 0.226

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.154 AC: 224038 AN: 1457726 Hom.: 22680 Cov.: 32 AF XY: 0.156 AC XY: 113080 AN XY: 725132

Gnomad4 AFR exome AF: 0.0208

Gnomad4 AMR exome AF: 0.347

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.545

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.136 AC: 20716 AN: 152108 Hom.: 2362 Cov.: 32 AF XY: 0.143 AC XY: 10622 AN XY: 74330

Gnomad4 AFR AF: 0.0286

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.134

Alfa AF: 0.141 Hom.: 3052

Bravo AF: 0.141

Asia WGS AF: 0.295 AC: 1024 AN: 3478

EpiCase AF: 0.141

EpiControl AF: 0.139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	0.15
Dann	Benign	0.73

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: rs2072546; hg19: chr7-107872816; COSMIC: COSV61037084; COSMIC: COSV61037084;