rs6802458

chr3-56388743-C-T

Variant summary

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

The NM_015576.3(ERC2):c.657+45608G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 151,916 control chromosomes in the GnomAD database, including 29,023 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 0.61 (29023 hom., cov: 31)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287

Genes affected

ERC2 (HGNC:31922): (ELKS/RAB6-interacting/CAST family member 2) This gene encodes a protein that belongs to the Rab3-interacting molecule (RIM)-binding protein family. Members of this protein family form part of the cytomatrix at the active zone (CAZ) complex and function as regulators of neurotransmitter release. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERC2	NM_015576.3	c.657+45608G>A		intron_variant		ENST00000288221.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERC2	ENST00000288221.11	c.657+45608G>A		intron_variant		1	NM_015576.3	P1
ERC2	ENST00000460849.5	c.657+45608G>A		intron_variant, NMD_transcript_variant		1
ERC2	ENST00000492584.3	c.657+45608G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93033 AN: 151800 Hom.: 29010 Cov.: 31

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.613 AC: 93075 AN: 151916 Hom.: 29023 Cov.: 31 AF XY: 0.614 AC XY: 45558 AN XY: 74254

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.633

Alfa AF: 0.639 Hom.: 17640

Bravo AF: 0.607

Asia WGS AF: 0.767 AC: 2663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.7
Dann	Benign	0.80

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: rs6802458; hg19: chr3-56422771;