3-56388878-C-G

Position:

• chr3-56388878-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015576.3(ERC2):​c.657+45473G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,956 control chromosomes in the GnomAD database, including 8,745 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 0.34 (8745 hom., cov: 32)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134

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]

ERC2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERC2	NM_015576.3	c.657+45473G>C		intron_variant		ENST00000288221.11	NP_056391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERC2	ENST00000288221.11	c.657+45473G>C		intron_variant		1	NM_015576.3	ENSP00000288221.6
ERC2	ENST00000460849.5	n.657+45473G>C		intron_variant		1		ENSP00000417445.1
ERC2	ENST00000492584.3	c.657+45473G>C		intron_variant		5		ENSP00000417280.3

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50914 AN: 151838 Hom.: 8722 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.335 AC: 50978 AN: 151956 Hom.: 8745 Cov.: 32 AF XY: 0.335 AC XY: 24869 AN XY: 74236

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.326

Alfa AF: 0.310 Hom.: 890

Bravo AF: 0.338

Asia WGS AF: 0.219 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.40

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: rs4974210; hg19: chr3-56422906;