rs1034825

Variant names:

• chr7-108443061-C-T
• rs1034825
• NM_001037132.4:c.-332+13182G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

NRCAM Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with neuromuscular and skeletal abnormalities

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.-332+13182G>A		intron_variant	Intron 1 of 32	ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.-332+13182G>A		intron_variant	Intron 1 of 32	5	NM_001037132.4	ENSP00000368314.3

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

African (AFR) AF: 0.729 AC: 30252 AN: 41482

American (AMR) AF: 0.537 AC: 8201 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1677 AN: 3460

East Asian (EAS) AF: 0.480 AC: 2485 AN: 5172

South Asian (SAS) AF: 0.515 AC: 2479 AN: 4814

European-Finnish (FIN) AF: 0.567 AC: 5987 AN: 10550

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.567 AC: 38517 AN: 67924

Other (OTH) AF: 0.557 AC: 1179 AN: 2116

Alfa AF: 0.576 Hom.: 7542

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
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1034825; hg19: chr7-108083505;