rs441534

Variant names:

• chr7-108189092-G-A
• rs441534
• NM_001037132.4:c.2035+553C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with neuromuscular and skeletal abnormalities

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.2035+553C>T		intron_variant	Intron 20 of 32	ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.2035+553C>T		intron_variant	Intron 20 of 32	5	NM_001037132.4	ENSP00000368314.3
NRCAM	ENST00000379024.8	c.1978+553C>T		intron_variant	Intron 19 of 29	1		ENSP00000368310.4
NRCAM	ENST00000351718.8	c.1987+553C>T		intron_variant	Intron 18 of 27	1		ENSP00000325269.6
NRCAM	ENST00000413765.6	c.2035+553C>T		intron_variant	Intron 20 of 30	2		ENSP00000407858.3

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

African (AFR) AF: 0.521 AC: 21536 AN: 41354

American (AMR) AF: 0.779 AC: 11883 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2478 AN: 3466

East Asian (EAS) AF: 0.957 AC: 4861 AN: 5082

South Asian (SAS) AF: 0.731 AC: 3510 AN: 4804

European-Finnish (FIN) AF: 0.745 AC: 7851 AN: 10544

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.773 AC: 52547 AN: 67940

Other (OTH) AF: 0.710 AC: 1495 AN: 2106

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
PhyloP100		-0.097
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs441534; hg19: chr7-107829536;