rs9311594

Positions:

• chr3-56098622-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.1474-17638C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,154 control chromosomes in the GnomAD database, including 2,364 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 0.17 (2364 hom., cov: 32)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.623

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERC2	NM_015576.3	c.1474-17638C>T		intron_variant		ENST00000288221.11	NP_056391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERC2	ENST00000288221.11	c.1474-17638C>T		intron_variant		1	NM_015576.3	ENSP00000288221	P1
ERC2	ENST00000460849.5	c.1474-17638C>T		intron_variant, NMD_transcript_variant		1		ENSP00000417445
ERC2	ENST00000492584.3	c.1474-17638C>T		intron_variant		5		ENSP00000417280

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25845 AN: 152036 Hom.: 2358 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0753

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.170 AC: 25882 AN: 152154 Hom.: 2364 Cov.: 32 AF XY: 0.167 AC XY: 12399 AN XY: 74386

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.0753

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.188

Alfa AF: 0.139 Hom.: 777

Bravo AF: 0.179

Asia WGS AF: 0.165 AC: 572 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.49

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: rs9311594; hg19: chr3-56132650;