7-108442655-C-T

Variant names:

• chr7-108442655-C-T
• rs2041001
• NM_001037132.4:c.-332+13588G>A

Variant summary

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

The NM_001037132.4(NRCAM):​c.-332+13588G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.949 in 152,314 control chromosomes in the GnomAD database, including 68,678 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 0.95 (68678 hom., cov: 33)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.-332+13588G>A		intron_variant	Intron 1 of 32	ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.-332+13588G>A		intron_variant	Intron 1 of 32	5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes AF: 0.949 AC: 144381 AN: 152196 Hom.: 68628 Cov.: 33

Gnomad AFR AF: 0.989

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.921

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.884

Gnomad FIN AF: 0.944

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.952

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

GnomAD4 genome AF: 0.949 AC: 144487 AN: 152314 Hom.: 68678 Cov.: 33 AF XY: 0.946 AC XY: 70469 AN XY: 74480

African (AFR) AF: 0.989 AC: 41099 AN: 41572

American (AMR) AF: 0.929 AC: 14215 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.921 AC: 3197 AN: 3472

East Asian (EAS) AF: 0.776 AC: 4013 AN: 5174

South Asian (SAS) AF: 0.884 AC: 4265 AN: 4824

European-Finnish (FIN) AF: 0.944 AC: 10026 AN: 10618

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.949 AC: 64561 AN: 68036

Other (OTH) AF: 0.946 AC: 2001 AN: 2116

Alfa AF: 0.946 Hom.: 130284

Bravo AF: 0.949

Asia WGS AF: 0.850 AC: 2957 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	1.4
DANN	Benign	0.68
PhyloP100		-0.018
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: rs2041001; hg19: chr7-108083099;