7-108409583-C-T

Variant names:

• chr7-108409583-C-T
• rs2300039
• NM_001037132.4:c.-331-9990G>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.-331-9990G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,112 control chromosomes in the GnomAD database, including 22,494 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 0.52 (22494 hom., cov: 32)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.694
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.-331-9990G>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.-331-9990G>A		intron_variant	Intron 1 of 32	5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78698 AN: 151992 Hom.: 22487 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.518 AC: 78731 AN: 152112 Hom.: 22494 Cov.: 32 AF XY: 0.529 AC XY: 39338 AN XY: 74354

African (AFR) AF: 0.263 AC: 10916 AN: 41512

American (AMR) AF: 0.641 AC: 9796 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2333 AN: 3470

East Asian (EAS) AF: 0.772 AC: 3985 AN: 5164

South Asian (SAS) AF: 0.779 AC: 3757 AN: 4822

European-Finnish (FIN) AF: 0.635 AC: 6709 AN: 10564

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39429 AN: 67976

Other (OTH) AF: 0.552 AC: 1166 AN: 2112

Alfa AF: 0.567 Hom.: 23295

Bravo AF: 0.507

Asia WGS AF: 0.745 AC: 2589 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	2.3
DANN	Benign	0.49
PhyloP100		-0.69
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: rs2300039; hg19: chr7-108050027;