rs3907611

Positions:

• chr3-55572080-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.*40-60804C>T variant causes a intron change. The variant allele was found at a frequency of 0.0605 in 152,332 control chromosomes in the GnomAD database, including 384 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 0.061 (384 hom., cov: 32)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28

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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERC2	NM_015576.3	c.*40-60804C>T		intron_variant		ENST00000288221.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERC2	ENST00000288221.11	c.*40-60804C>T		intron_variant		1	NM_015576.3	P1

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9218 AN: 152214 Hom.: 384 Cov.: 32

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0495

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0486

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0875

Gnomad OTH AF: 0.0693

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

GnomAD4 genome AF: 0.0605 AC: 9219 AN: 152332 Hom.: 384 Cov.: 32 AF XY: 0.0599 AC XY: 4459 AN XY: 74490

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.0495

Gnomad4 ASJ AF: 0.0308

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0488

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.0875

Gnomad4 OTH AF: 0.0686

Alfa AF: 0.0788 Hom.: 253

Bravo AF: 0.0544

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.77

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: rs3907611; hg19: chr3-55606108;