7-108447879-A-T

Position:

• chr7-108447879-A-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+8364T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,976 control chromosomes in the GnomAD database, including 9,809 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 0.35 (9809 hom., cov: 32)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.-332+8364T>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+8364T>A		intron_variant		5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53220 AN: 151858 Hom.: 9788 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.351 AC: 53292 AN: 151976 Hom.: 9809 Cov.: 32 AF XY: 0.355 AC XY: 26368 AN XY: 74258

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.322

Alfa AF: 0.169 Hom.: 326

Bravo AF: 0.353

Asia WGS AF: 0.365 AC: 1266 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.52

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: rs1859767; hg19: chr7-108088323;