rs17330779

Positions:

• chr7-108243255-C-A
• chr7-108243255-C-T

Variant summary

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

The NM_001037132.4(NRCAM):​c.-106-3085G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0404 in 152,218 control chromosomes in the GnomAD database, including 167 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 0.040 (167 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.811

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.-106-3085G>T		intron_variant		ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.-106-3085G>T		intron_variant		5	NM_001037132.4	ENSP00000368314	P1

Frequencies

GnomAD3 genomes AF: 0.0404 AC: 6145 AN: 152100 Hom.: 167 Cov.: 32

Gnomad AFR AF: 0.00985

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.0744

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0567

Gnomad OTH AF: 0.0512

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 38 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 34

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0404 AC: 6148 AN: 152218 Hom.: 167 Cov.: 32 AF XY: 0.0411 AC XY: 3058 AN XY: 74410

Gnomad4 AFR AF: 0.00982

Gnomad4 AMR AF: 0.0321

Gnomad4 ASJ AF: 0.0697

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.0744

Gnomad4 NFE AF: 0.0568

Gnomad4 OTH AF: 0.0507

Alfa AF: 0.0317 Hom.: 26

Bravo AF: 0.0359

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.36
DANN	Benign	0.49

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: rs17330779; hg19: chr7-107883699;