3-56148637-C-T

Variant names:

• chr3-56148637-C-T
• rs6788505
• NM_015576.3:c.1305+340G>A

Variant summary

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

The NM_015576.3(ERC2):​c.1305+340G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 152,048 control chromosomes in the GnomAD database, including 282 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 0.057 (282 hom., cov: 33)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERC2	NM_015576.3	c.1305+340G>A		intron_variant	Intron 5 of 17	ENST00000288221.11	NP_056391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERC2	ENST00000288221.11	c.1305+340G>A		intron_variant	Intron 5 of 17	1	NM_015576.3	ENSP00000288221.6
ERC2	ENST00000460849.5	n.1305+340G>A		intron_variant	Intron 5 of 18	1		ENSP00000417445.1
ERC2	ENST00000492584.3	c.1305+340G>A		intron_variant	Intron 5 of 17	5		ENSP00000417280.3

Frequencies

GnomAD3 genomes AF: 0.0569 AC: 8648 AN: 151930 Hom.: 277 Cov.: 33

Gnomad AFR AF: 0.0945

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0360

Gnomad ASJ AF: 0.0589

Gnomad EAS AF: 0.0272

Gnomad SAS AF: 0.0626

Gnomad FIN AF: 0.0177

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0464

Gnomad OTH AF: 0.0632

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

GnomAD4 genome AF: 0.0570 AC: 8674 AN: 152048 Hom.: 282 Cov.: 33 AF XY: 0.0555 AC XY: 4122 AN XY: 74302

African (AFR) AF: 0.0949 AC: 3932 AN: 41446

American (AMR) AF: 0.0359 AC: 549 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0589 AC: 204 AN: 3466

East Asian (EAS) AF: 0.0273 AC: 141 AN: 5170

South Asian (SAS) AF: 0.0624 AC: 301 AN: 4822

European-Finnish (FIN) AF: 0.0177 AC: 187 AN: 10562

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0464 AC: 3158 AN: 67988

Other (OTH) AF: 0.0649 AC: 137 AN: 2112

Alfa AF: 0.0322 Hom.: 33

Bravo AF: 0.0598

Asia WGS AF: 0.0590 AC: 210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.070
DANN	Benign	0.65
PhyloP100		-1.7
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: rs6788505; hg19: chr3-56182665;