7-108230187-A-G

Position:

• chr7-108230187-A-G

Variant summary

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

The NM_001037132.4(NRCAM):​c.550+844T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,684 control chromosomes in the GnomAD database, including 13,975 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 0.40 (13975 hom., cov: 30)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRCAM	NM_001037132.4	c.550+844T>C		intron_variant		ENST00000379028.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRCAM	ENST00000379028.8	c.550+844T>C		intron_variant		5	NM_001037132.4	P1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60138 AN: 151564 Hom.: 13984 Cov.: 30

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.396 AC: 60135 AN: 151684 Hom.: 13975 Cov.: 30 AF XY: 0.404 AC XY: 29891 AN XY: 74052

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.828

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.416

Alfa AF: 0.450 Hom.: 11465

Bravo AF: 0.399

Asia WGS AF: 0.585 AC: 2032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.10
DANN	Benign	0.53

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: rs1269629; hg19: chr7-107870631;