7-108240168-A-G

Position:

• chr7-108240168-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.-104T>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 705,728 control chromosomes in the GnomAD database, including 84,132 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (14409 hom., cov: 32)
  • Exomes 𝑓: 0.49 (69723 hom.)
• Consequence: NRCAM NM_001037132.4 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.-104T>C		splice_region_variant	4/33	ENST00000379028.8	NP_001032209.1
NRCAM	NM_001037132.4	c.-104T>C		5_prime_UTR_variant	4/33	ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.-104T>C		splice_region_variant	4/33	5	NM_001037132.4	ENSP00000368314.3
NRCAM	ENST00000379028.8	c.-104T>C		5_prime_UTR_variant	4/33	5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60344 AN: 151956 Hom.: 14416 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.421

GnomAD4 exome AF: 0.486 AC: 269039 AN: 553652 Hom.: 69723 Cov.: 7 AF XY: 0.486 AC XY: 143832 AN XY: 296094

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.632

Gnomad4 ASJ exome AF: 0.538

Gnomad4 EAS exome AF: 0.830

Gnomad4 SAS exome AF: 0.491

Gnomad4 FIN exome AF: 0.436

Gnomad4 NFE exome AF: 0.460

Gnomad4 OTH exome AF: 0.469

GnomAD4 genome AF: 0.397 AC: 60339 AN: 152076 Hom.: 14409 Cov.: 32 AF XY: 0.404 AC XY: 30035 AN XY: 74332

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.828

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.422

Alfa AF: 0.467 Hom.: 26261

Bravo AF: 0.398

Asia WGS AF: 0.587 AC: 2038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.3
DANN	Benign	0.65

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: rs1269634; hg19: chr7-107880612; COSMIC: COSV61034793; COSMIC: COSV61034793;