rs12539530

Variant names:

• chr7-108336117-G-A
• rs12539530
• NM_001037132.4:c.-173-23386C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001037132.4(NRCAM):​c.-173-23386C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,900 control chromosomes in the GnomAD database, including 6,790 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 0.29 (6790 hom., cov: 31)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.-173-23386C>T		intron_variant	Intron 2 of 32	ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.-173-23386C>T		intron_variant	Intron 2 of 32	5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43680 AN: 151782 Hom.: 6787 Cov.: 31

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.288 AC: 43696 AN: 151900 Hom.: 6790 Cov.: 31 AF XY: 0.297 AC XY: 22036 AN XY: 74212

African (AFR) AF: 0.226 AC: 9368 AN: 41420

American (AMR) AF: 0.344 AC: 5254 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1076 AN: 3470

East Asian (EAS) AF: 0.559 AC: 2879 AN: 5150

South Asian (SAS) AF: 0.448 AC: 2157 AN: 4816

European-Finnish (FIN) AF: 0.340 AC: 3575 AN: 10522

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18410 AN: 67934

Other (OTH) AF: 0.296 AC: 624 AN: 2108

Alfa AF: 0.280 Hom.: 17374

Bravo AF: 0.287

Asia WGS AF: 0.434 AC: 1506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	6.2
DANN	Benign	0.72
PhyloP100		-0.36
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: rs12539530; hg19: chr7-107976561;