7-108332853-A-G

Position:

• chr7-108332853-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.-173-20122T>C		intron_variant		ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.-173-20122T>C		intron_variant		5	NM_001037132.4	ENSP00000368314	P1

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

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.299

Alfa AF: 0.292 Hom.: 1174

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6975557; hg19: chr7-107973297;