rs6790858

Positions:

• chr3-56335835-A-G

Variant summary

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

The ENST00000288221.11(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 ENST00000288221.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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=-0.84).
• 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/exons	MANE	Protein	UniProt
ERC2	NM_015576.3	c.658-39400T>C		intron_variant		ENST00000288221.11	NP_056391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERC2	ENST00000288221.11	c.658-39400T>C		intron_variant		1	NM_015576.3	ENSP00000288221	P1
ERC2	ENST00000460849.5	c.658-39400T>C		intron_variant, NMD_transcript_variant		1		ENSP00000417445
ERC2	ENST00000492584.3	c.658-39400T>C		intron_variant		5		ENSP00000417280

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

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.236

Alfa AF: 0.270 Hom.: 1758

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

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: rs6790858; hg19: chr3-56369863;