7-108201288-C-T

Variant names:

• chr7-108201288-C-T
• rs405945
• NM_001037132.4:c.1208-3189G>A

Variant summary

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

The NM_001037132.4(NRCAM):​c.1208-3189G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,836 control chromosomes in the GnomAD database, including 13,463 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 0.38 (13463 hom., cov: 31)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.1208-3189G>A		intron_variant	Intron 13 of 32	ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.1208-3189G>A		intron_variant	Intron 13 of 32	5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58116 AN: 151738 Hom.: 13470 Cov.: 31

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.383 AC: 58112 AN: 151836 Hom.: 13463 Cov.: 31 AF XY: 0.391 AC XY: 28991 AN XY: 74160

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.403

Alfa AF: 0.419 Hom.: 2898

Bravo AF: 0.383

Asia WGS AF: 0.565 AC: 1961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.79
DANN	Benign	0.62

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: rs405945; hg19: chr7-107841732;