rs441534

Positions:

• chr7-108189092-G-A
• chr7-108189092-G-C

Variant summary

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

The NM_001037132.4(NRCAM):​c.2035+553C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 151,756 control chromosomes in the GnomAD database, including 39,034 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 0.71 (39034 hom., cov: 30)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.2035+553C>T		intron_variant		ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.2035+553C>T		intron_variant		5	NM_001037132.4	ENSP00000368314	P1
NRCAM	ENST00000351718.8	c.1987+553C>T		intron_variant		1		ENSP00000325269
NRCAM	ENST00000379024.8	c.1978+553C>T		intron_variant		1		ENSP00000368310
NRCAM	ENST00000413765.6	c.2035+553C>T		intron_variant		2		ENSP00000407858

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107053 AN: 151638 Hom.: 39015 Cov.: 30

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.706 AC: 107114 AN: 151756 Hom.: 39034 Cov.: 30 AF XY: 0.708 AC XY: 52454 AN XY: 74122

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.779

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.745

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.710

Alfa AF: 0.739 Hom.: 5845

Bravo AF: 0.702

Asia WGS AF: 0.802 AC: 2791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.71

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: rs441534; hg19: chr7-107829536;