chr7-108184445-C-G

Position:

• chr7-108184445-C-G

Variant summary

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

The NM_001037132.4(NRCAM):​c.2205G>C​(p.Ala735=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,613,832 control chromosomes in the GnomAD database, including 472,088 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 0.68 (37216 hom., cov: 33)
  • Exomes 𝑓: 0.77 (434872 hom.)
• Consequence: NRCAM NM_001037132.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20

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=-0.85).
• BP7: Synonymous conserved (PhyloP=-2.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.2205G>C	p.Ala735=	synonymous_variant	21/33	ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.2205G>C	p.Ala735=	synonymous_variant	21/33	5	NM_001037132.4	ENSP00000368314	P1
NRCAM	ENST00000379024.8	c.2148G>C	p.Ala716=	synonymous_variant	20/30	1		ENSP00000368310
NRCAM	ENST00000351718.8	c.2157G>C	p.Ala719=	synonymous_variant	19/28	1		ENSP00000325269
NRCAM	ENST00000413765.6	c.2205G>C	p.Ala735=	synonymous_variant	21/31	2		ENSP00000407858

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103367 AN: 152014 Hom.: 37206 Cov.: 33

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.685

GnomAD3 exomes AF: 0.760 AC: 190785 AN: 251116 Hom.: 74108 AF XY: 0.761 AC XY: 103301 AN XY: 135780

Gnomad AFR exome AF: 0.422

Gnomad AMR exome AF: 0.827

Gnomad ASJ exome AF: 0.710

Gnomad EAS exome AF: 0.971

Gnomad SAS exome AF: 0.729

Gnomad FIN exome AF: 0.750

Gnomad NFE exome AF: 0.768

Gnomad OTH exome AF: 0.755

GnomAD4 exome AF: 0.768 AC: 1122989 AN: 1461700 Hom.: 434872 Cov.: 54 AF XY: 0.768 AC XY: 558128 AN XY: 727174

Gnomad4 AFR exome AF: 0.416

Gnomad4 AMR exome AF: 0.817

Gnomad4 ASJ exome AF: 0.710

Gnomad4 EAS exome AF: 0.951

Gnomad4 SAS exome AF: 0.734

Gnomad4 FIN exome AF: 0.755

Gnomad4 NFE exome AF: 0.777

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.680 AC: 103411 AN: 152132 Hom.: 37216 Cov.: 33 AF XY: 0.683 AC XY: 50825 AN XY: 74376

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.960

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.688

Alfa AF: 0.744 Hom.: 13910

Bravo AF: 0.672

Asia WGS AF: 0.796 AC: 2767 AN: 3478

EpiCase AF: 0.767

EpiControl AF: 0.760

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.028
DANN	Benign	0.44

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: rs401433; hg19: chr7-107824889; COSMIC: COSV105261822;