rs9311594

Variant names:

• chr3-56098622-G-A
• rs9311594
• NM_015576.3:c.1474-17638C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015576.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERC2	NM_015576.3	MANE Select	c.1474-17638C>T		intron	N/A	NP_056391.1	O15083
	ERC2	NR_132749.2		n.1834-17638C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERC2	ENST00000288221.11	TSL:1 MANE Select	c.1474-17638C>T		intron	N/A	ENSP00000288221.6	O15083
	ERC2	ENST00000460849.5	TSL:1	n.1474-17638C>T		intron	N/A	ENSP00000417445.1	O15083
	ERC2	ENST00000940588.1		c.1516-17638C>T		intron	N/A	ENSP00000610647.1

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

African (AFR) AF: 0.226 AC: 9378 AN: 41480

American (AMR) AF: 0.155 AC: 2364 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 684 AN: 3472

East Asian (EAS) AF: 0.181 AC: 938 AN: 5172

South Asian (SAS) AF: 0.150 AC: 723 AN: 4822

European-Finnish (FIN) AF: 0.0753 AC: 799 AN: 10610

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10460 AN: 67996

Other (OTH) AF: 0.188 AC: 397 AN: 2112

Alfa AF: 0.142 Hom.: 900

Bravo AF: 0.179

Asia WGS AF: 0.165 AC: 572 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.49
PhyloP100		0.62
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: rs9311594; hg19: chr3-56132650;