rs6790858

Variant names:

• chr3-56335835-A-G
• rs6790858
• NM_015576.3:c.658-39400T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015576.3(ERC2):​c.658-39400T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,018 control chromosomes in the GnomAD database, including 4,945 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 0.25 (4945 hom., cov: 32)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERC2	NM_015576.3	c.658-39400T>C		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.658-39400T>C		intron_variant	Intron 2 of 17	1	NM_015576.3	ENSP00000288221.6
ERC2	ENST00000460849.5	n.658-39400T>C		intron_variant	Intron 2 of 18	1		ENSP00000417445.1
ERC2	ENST00000492584.3	c.658-39400T>C		intron_variant	Intron 2 of 17	5		ENSP00000417280.3

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37265 AN: 151900 Hom.: 4932 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.245 AC: 37302 AN: 152018 Hom.: 4945 Cov.: 32 AF XY: 0.247 AC XY: 18370 AN XY: 74298

African (AFR) AF: 0.151 AC: 6281 AN: 41488

American (AMR) AF: 0.293 AC: 4478 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 749 AN: 3468

East Asian (EAS) AF: 0.137 AC: 709 AN: 5186

South Asian (SAS) AF: 0.179 AC: 857 AN: 4798

European-Finnish (FIN) AF: 0.319 AC: 3367 AN: 10542

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19978 AN: 67964

Other (OTH) AF: 0.236 AC: 498 AN: 2110

Alfa AF: 0.267 Hom.: 2172

Bravo AF: 0.239

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.62
PhyloP100		1.0
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: rs6790858; hg19: chr3-56369863;