rs2216259

chr7-108375106-A-Cchr7-108375106-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001037132.4(NRCAM):c.-174+24330T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,842 control chromosomes in the GnomAD database, including 8,754 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 0.33 (8754 hom., cov: 31)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRCAM	NM_001037132.4	c.-174+24330T>G		intron_variant		ENST00000379028.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRCAM	ENST00000379028.8	c.-174+24330T>G		intron_variant		5	NM_001037132.4	P1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49992 AN: 151722 Hom.: 8737 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.330 AC: 50042 AN: 151842 Hom.: 8754 Cov.: 31 AF XY: 0.336 AC XY: 24967 AN XY: 74212

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.325

Alfa AF: 0.300 Hom.: 931

Bravo AF: 0.335

Asia WGS AF: 0.458 AC: 1589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.11
Dann	Benign	0.46

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: rs2216259; hg19: chr7-108015550;