rs2300043

Positions:

• chr7-108422651-G-C
• chr7-108422651-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001037132.4(NRCAM):​c.-331-23058C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,774 control chromosomes in the GnomAD database, including 9,161 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 0.34 (9161 hom., cov: 32)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRCAM	NM_001037132.4	c.-331-23058C>G		intron_variant		ENST00000379028.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRCAM	ENST00000379028.8	c.-331-23058C>G		intron_variant		5	NM_001037132.4	P1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51046 AN: 151656 Hom.: 9157 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.336 AC: 51061 AN: 151774 Hom.: 9161 Cov.: 32 AF XY: 0.341 AC XY: 25331 AN XY: 74224

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.380

Alfa AF: 0.353 Hom.: 1242

Bravo AF: 0.334

Asia WGS AF: 0.501 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
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: rs2300043; hg19: chr7-108063095;