rs1034825

Positions:

• chr7-108443061-C-T

Variant summary

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

The NM_001037132.4(NRCAM):​c.-332+13182G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 152,004 control chromosomes in the GnomAD database, including 27,904 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 0.60 (27904 hom., cov: 33)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.-332+13182G>A		intron_variant		ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.-332+13182G>A		intron_variant		5	NM_001037132.4	ENSP00000368314	P1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91254 AN: 151886 Hom.: 27862 Cov.: 33

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.601 AC: 91350 AN: 152004 Hom.: 27904 Cov.: 33 AF XY: 0.598 AC XY: 44426 AN XY: 74282

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.557

Alfa AF: 0.585 Hom.: 3280

Bravo AF: 0.601

Asia WGS AF: 0.479 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.41

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: rs1034825; hg19: chr7-108083505;