rs6802458

Variant names:

• chr3-56388743-C-T
• rs6802458
• NM_015576.3:c.657+45608G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ERC2	NM_015576.3	c.657+45608G>A		intron_variant	Intron 2 of 17	ENST00000288221.11	NP_056391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERC2	ENST00000288221.11	c.657+45608G>A		intron_variant	Intron 2 of 17	1	NM_015576.3	ENSP00000288221.6
ERC2	ENST00000460849.5	n.657+45608G>A		intron_variant	Intron 2 of 18	1		ENSP00000417445.1
ERC2	ENST00000492584.3	c.657+45608G>A		intron_variant	Intron 2 of 17	5		ENSP00000417280.3

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

African (AFR) AF: 0.506 AC: 20951 AN: 41390

American (AMR) AF: 0.634 AC: 9676 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2491 AN: 3468

East Asian (EAS) AF: 0.846 AC: 4361 AN: 5156

South Asian (SAS) AF: 0.744 AC: 3587 AN: 4822

European-Finnish (FIN) AF: 0.628 AC: 6633 AN: 10558

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.637 AC: 43314 AN: 67944

Other (OTH) AF: 0.633 AC: 1335 AN: 2108

Alfa AF: 0.637 Hom.: 19266

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
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6802458; hg19: chr3-56422771;