rs10510779

Positions:

• chr3-56076995-T-C

Variant summary

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

The NM_015576.3(ERC2):​c.1641+3822A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,148 control chromosomes in the GnomAD database, including 1,455 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 0.13 (1455 hom., cov: 32)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.418

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]

ERC2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERC2	NM_015576.3	c.1641+3822A>G		intron_variant		ENST00000288221.11	NP_056391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERC2	ENST00000288221.11	c.1641+3822A>G		intron_variant		1	NM_015576.3	ENSP00000288221.6
ERC2	ENST00000460849.5	n.1641+3822A>G		intron_variant		1		ENSP00000417445.1
ERC2	ENST00000492584.3	c.1641+3822A>G		intron_variant		5		ENSP00000417280.3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20336 AN: 152030 Hom.: 1456 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0690

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.134 AC: 20332 AN: 152148 Hom.: 1455 Cov.: 32 AF XY: 0.130 AC XY: 9709 AN XY: 74410

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0690

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.152

Alfa AF: 0.139 Hom.: 216

Bravo AF: 0.139

Asia WGS AF: 0.127 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.2
DANN	Benign	0.55

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: rs10510779; hg19: chr3-56111023;