rs414077

Positions:

• chr7-108180467-G-T

Variant summary

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

The NM_001037132.4(NRCAM):​c.2647-40C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 1,520,280 control chromosomes in the GnomAD database, including 628,355 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 0.91 (62976 hom., cov: 34)
  • Exomes 𝑓: 0.91 (565379 hom.)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

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 = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRCAM	NM_001037132.4	c.2647-40C>A		intron_variant		ENST00000379028.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRCAM	ENST00000379028.8	c.2647-40C>A		intron_variant		5	NM_001037132.4	P1
NRCAM	ENST00000351718.8	c.2599-40C>A		intron_variant		1
NRCAM	ENST00000379024.8	c.2590-40C>A		intron_variant		1
NRCAM	ENST00000413765.6	c.2647-40C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.909 AC: 138381 AN: 152192 Hom.: 62927 Cov.: 34

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.926

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.924

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.907

GnomAD3 exomes AF: 0.919 AC: 225666 AN: 245556 Hom.: 103809 AF XY: 0.917 AC XY: 121682 AN XY: 132768

Gnomad AFR exome AF: 0.900

Gnomad AMR exome AF: 0.952

Gnomad ASJ exome AF: 0.924

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.894

Gnomad FIN exome AF: 0.922

Gnomad NFE exome AF: 0.904

Gnomad OTH exome AF: 0.921

GnomAD4 exome AF: 0.909 AC: 1243405 AN: 1367970 Hom.: 565379 Cov.: 19 AF XY: 0.908 AC XY: 623043 AN XY: 685950

Gnomad4 AFR exome AF: 0.896

Gnomad4 AMR exome AF: 0.948

Gnomad4 ASJ exome AF: 0.925

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.897

Gnomad4 FIN exome AF: 0.923

Gnomad4 NFE exome AF: 0.904

Gnomad4 OTH exome AF: 0.912

GnomAD4 genome AF: 0.909 AC: 138488 AN: 152310 Hom.: 62976 Cov.: 34 AF XY: 0.910 AC XY: 67798 AN XY: 74480

Gnomad4 AFR AF: 0.896

Gnomad4 AMR AF: 0.926

Gnomad4 ASJ AF: 0.933

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.895

Gnomad4 FIN AF: 0.924

Gnomad4 NFE AF: 0.905

Gnomad4 OTH AF: 0.908

Alfa AF: 0.905 Hom.: 75172

Bravo AF: 0.909

Asia WGS AF: 0.951 AC: 3307 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	0.95
DANN	Benign	0.70

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: rs414077; hg19: chr7-107820911;