chr3-55924031-T-G

Variant names:

• chr3-55924031-T-G
• rs724333
• NM_015576.3:c.2403+26394A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015576.3(ERC2):​c.2403+26394A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 152,038 control chromosomes in the GnomAD database, including 39,222 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 0.72 (39222 hom., cov: 32)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.764 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERC2	NM_015576.3	MANE Select	c.2403+26394A>C		intron	N/A	NP_056391.1
	ERC2	NR_132749.2		n.2763+26394A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERC2	ENST00000288221.11	TSL:1 MANE Select	c.2403+26394A>C		intron	N/A	ENSP00000288221.6
	ERC2	ENST00000460849.5	TSL:1	n.2403+26394A>C		intron	N/A	ENSP00000417445.1
	ERC2	ENST00000492584.3	TSL:5	c.2427+26394A>C		intron	N/A	ENSP00000417280.3

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108776 AN: 151920 Hom.: 39182 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.701

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

GnomAD4 genome AF: 0.716 AC: 108867 AN: 152038 Hom.: 39222 Cov.: 32 AF XY: 0.725 AC XY: 53847 AN XY: 74318

African (AFR) AF: 0.695 AC: 28794 AN: 41444

American (AMR) AF: 0.776 AC: 11850 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2163 AN: 3472

East Asian (EAS) AF: 0.680 AC: 3501 AN: 5148

South Asian (SAS) AF: 0.618 AC: 2974 AN: 4814

European-Finnish (FIN) AF: 0.832 AC: 8815 AN: 10594

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.710 AC: 48259 AN: 67978

Other (OTH) AF: 0.702 AC: 1483 AN: 2112

Alfa AF: 0.725 Hom.: 5171

Bravo AF: 0.709

Asia WGS AF: 0.615 AC: 2139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.44
PhyloP100		0.58
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: rs724333; hg19: chr3-55958059;