7-108332853-A-G

Variant names:

• chr7-108332853-A-G
• rs6975557
• NM_001037132.4:c.-173-20122T>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.-173-20122T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,054 control chromosomes in the GnomAD database, including 7,047 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 (7047 hom., cov: 32)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.-173-20122T>C		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.-173-20122T>C		intron_variant	Intron 2 of 32	5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44760 AN: 151936 Hom.: 7040 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.295 AC: 44796 AN: 152054 Hom.: 7047 Cov.: 32 AF XY: 0.303 AC XY: 22545 AN XY: 74308

African (AFR) AF: 0.251 AC: 10411 AN: 41480

American (AMR) AF: 0.347 AC: 5293 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1079 AN: 3468

East Asian (EAS) AF: 0.557 AC: 2868 AN: 5152

South Asian (SAS) AF: 0.446 AC: 2146 AN: 4810

European-Finnish (FIN) AF: 0.338 AC: 3570 AN: 10552

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18443 AN: 67996

Other (OTH) AF: 0.299 AC: 632 AN: 2116

Alfa AF: 0.293 Hom.: 9642

Bravo AF: 0.295

Asia WGS AF: 0.436 AC: 1513 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.61
PhyloP100		0.073
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: rs6975557; hg19: chr7-107973297;