rs3907611

Variant names:

• chr3-55572080-G-A
• rs3907611
• NM_015576.3:c.*40-60804C>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.*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
• Publications: 3 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]

ENSG00000306397 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.*40-60804C>T		intron	N/A	NP_056391.1	O15083
	ERC2	NR_132749.2		n.3460+34700C>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.*40-60804C>T		intron	N/A	ENSP00000288221.6	O15083
	ERC2	ENST00000460849.5	TSL:1	n.*226+34700C>T		intron	N/A	ENSP00000417445.1	O15083
	ERC2	ENST00000484530.5	TSL:1	n.551+34671C>T		intron	N/A

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

African (AFR) AF: 0.0173 AC: 719 AN: 41584

American (AMR) AF: 0.0495 AC: 758 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 107 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0488 AC: 236 AN: 4832

European-Finnish (FIN) AF: 0.117 AC: 1237 AN: 10610

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0875 AC: 5952 AN: 68028

Other (OTH) AF: 0.0686 AC: 145 AN: 2114

Alfa AF: 0.0791 Hom.: 274

Bravo AF: 0.0544

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.77
PhyloP100		4.3
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3907611;

hg19: chr3-55606108;