rs7644975

Positions:

• chr3-56371141-G-A

Variant summary

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

The NM_015576.3(ERC2):​c.657+63210C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,076 control chromosomes in the GnomAD database, including 4,660 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 0.23 (4660 hom., cov: 32)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

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 (NFE) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERC2	NM_015576.3	c.657+63210C>T		intron_variant		ENST00000288221.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERC2	ENST00000288221.11	c.657+63210C>T		intron_variant		1	NM_015576.3	P1
ERC2	ENST00000460849.5	c.657+63210C>T		intron_variant, NMD_transcript_variant		1
ERC2	ENST00000492584.3	c.657+63210C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35191 AN: 151960 Hom.: 4652 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.232 AC: 35216 AN: 152076 Hom.: 4660 Cov.: 32 AF XY: 0.233 AC XY: 17324 AN XY: 74350

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.222

Alfa AF: 0.250 Hom.: 967

Bravo AF: 0.223

Asia WGS AF: 0.145 AC: 505 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	2.8
DANN	Benign	0.69

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: rs7644975; hg19: chr3-56405169;