rs381828

Positions:

• chr7-108168522-A-C
• chr7-108168522-A-G
• chr7-108168522-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.3188-120T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 906,352 control chromosomes in the GnomAD database, including 305,192 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 0.72 (42032 hom., cov: 33)
  • Exomes 𝑓: 0.83 (263160 hom.)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545

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]

LOC102724363 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.3188-120T>G		intron_variant		ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.3188-120T>G		intron_variant		5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109844 AN: 152002 Hom.: 42039 Cov.: 33

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.738

GnomAD4 exome AF: 0.832 AC: 627405 AN: 754232 Hom.: 263160 AF XY: 0.832 AC XY: 305998 AN XY: 367836

Gnomad4 AFR exome AF: 0.427

Gnomad4 AMR exome AF: 0.808

Gnomad4 ASJ exome AF: 0.883

Gnomad4 EAS exome AF: 0.796

Gnomad4 SAS exome AF: 0.722

Gnomad4 FIN exome AF: 0.786

Gnomad4 NFE exome AF: 0.850

Gnomad4 OTH exome AF: 0.812

GnomAD4 genome AF: 0.722 AC: 109872 AN: 152120 Hom.: 42032 Cov.: 33 AF XY: 0.720 AC XY: 53521 AN XY: 74370

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.804

Gnomad4 ASJ AF: 0.887

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.757

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.737

Alfa AF: 0.778 Hom.: 5916

Bravo AF: 0.715

Asia WGS AF: 0.759 AC: 2640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.6
DANN	Benign	0.50

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: rs381828; hg19: chr7-107808967;