rs12537209

Variant names:

• chr7-108338705-G-A
• rs12537209
• NM_001037132.4:c.-173-25974C>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.-173-25974C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 151,880 control chromosomes in the GnomAD database, including 437 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 0.075 (437 hom., cov: 32)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249
• Publications: 0 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 = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.-173-25974C>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.-173-25974C>T		intron_variant	Intron 2 of 32	5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes AF: 0.0748 AC: 11356 AN: 151764 Hom.: 438 Cov.: 32

Gnomad AFR AF: 0.0886

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.0705

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0813

Gnomad FIN AF: 0.0787

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0638

Gnomad OTH AF: 0.0915

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

GnomAD4 genome AF: 0.0748 AC: 11364 AN: 151880 Hom.: 437 Cov.: 32 AF XY: 0.0768 AC XY: 5699 AN XY: 74230

African (AFR) AF: 0.0885 AC: 3667 AN: 41412

American (AMR) AF: 0.0706 AC: 1076 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 213 AN: 3468

East Asian (EAS) AF: 0.112 AC: 579 AN: 5164

South Asian (SAS) AF: 0.0811 AC: 389 AN: 4796

European-Finnish (FIN) AF: 0.0787 AC: 829 AN: 10540

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0638 AC: 4336 AN: 67936

Other (OTH) AF: 0.0910 AC: 192 AN: 2110

Alfa AF: 0.0711 Hom.: 55

Bravo AF: 0.0743

Asia WGS AF: 0.0980 AC: 340 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	1.7
DANN	Benign	0.11
PhyloP100		0.25
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: rs12537209; hg19: chr7-107979149;