NM_001037132.4:c.891-3288T>C

Variant names:

• chr7-108212893-A-G
• rs1269622
• NM_001037132.4:c.891-3288T>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.891-3288T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,046 control chromosomes in the GnomAD database, including 14,306 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 0.40 (14306 hom., cov: 31)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 1 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 (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.891-3288T>C		intron_variant	Intron 11 of 32	ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.891-3288T>C		intron_variant	Intron 11 of 32	5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60739 AN: 151928 Hom.: 14309 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.400 AC: 60743 AN: 152046 Hom.: 14306 Cov.: 31 AF XY: 0.407 AC XY: 30275 AN XY: 74328

African (AFR) AF: 0.160 AC: 6659 AN: 41522

American (AMR) AF: 0.545 AC: 8310 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1955 AN: 3466

East Asian (EAS) AF: 0.811 AC: 4191 AN: 5168

South Asian (SAS) AF: 0.478 AC: 2304 AN: 4818

European-Finnish (FIN) AF: 0.434 AC: 4584 AN: 10560

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31111 AN: 67958

Other (OTH) AF: 0.426 AC: 897 AN: 2106

Alfa AF: 0.412 Hom.: 1720

Bravo AF: 0.401

Asia WGS AF: 0.577 AC: 2004 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	5.3
DANN	Benign	0.67
PhyloP100		0.35
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: rs1269622; hg19: chr7-107853337;