NM_001037132.4:c.3677+2048C>T

Variant names:

• chr7-108157415-G-A
• rs409797
• NM_001037132.4:c.3677+2048C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001037132.4(NRCAM):​c.3677+2048C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,006 control chromosomes in the GnomAD database, including 30,084 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 0.58 (30084 hom., cov: 32)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 4 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=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.3677+2048C>T		intron_variant	Intron 32 of 32	ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.3677+2048C>T		intron_variant	Intron 32 of 32	5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88468 AN: 151888 Hom.: 30095 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.582 AC: 88463 AN: 152006 Hom.: 30084 Cov.: 32 AF XY: 0.584 AC XY: 43374 AN XY: 74290

African (AFR) AF: 0.203 AC: 8427 AN: 41452

American (AMR) AF: 0.716 AC: 10926 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2410 AN: 3468

East Asian (EAS) AF: 0.824 AC: 4272 AN: 5184

South Asian (SAS) AF: 0.624 AC: 3007 AN: 4820

European-Finnish (FIN) AF: 0.665 AC: 7024 AN: 10556

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.739 AC: 50197 AN: 67944

Other (OTH) AF: 0.605 AC: 1277 AN: 2110

Alfa AF: 0.570 Hom.: 4075

Bravo AF: 0.572

Asia WGS AF: 0.672 AC: 2338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	10
DANN	Benign	0.68
PhyloP100		1.3
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: rs409797; hg19: chr7-107797860;