chr3-56203389-G-A

Variant names:

• chr3-56203389-G-A
• rs4318528
• NM_015576.3:c.1075-29869C>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.1075-29869C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,998 control chromosomes in the GnomAD database, including 16,243 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 0.46 (16243 hom., cov: 33)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.459

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERC2	NM_015576.3	c.1075-29869C>T		intron_variant	Intron 3 of 17	ENST00000288221.11	NP_056391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERC2	ENST00000288221.11	c.1075-29869C>T		intron_variant	Intron 3 of 17	1	NM_015576.3	ENSP00000288221.6
ERC2	ENST00000460849.5	n.1075-29869C>T		intron_variant	Intron 3 of 18	1		ENSP00000417445.1
ERC2	ENST00000492584.3	c.1075-29869C>T		intron_variant	Intron 3 of 17	5		ENSP00000417280.3

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69163 AN: 151880 Hom.: 16238 Cov.: 33

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.455 AC: 69203 AN: 151998 Hom.: 16243 Cov.: 33 AF XY: 0.459 AC XY: 34097 AN XY: 74294

African (AFR) AF: 0.355 AC: 14712 AN: 41452

American (AMR) AF: 0.509 AC: 7762 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1472 AN: 3466

East Asian (EAS) AF: 0.709 AC: 3666 AN: 5170

South Asian (SAS) AF: 0.654 AC: 3147 AN: 4810

European-Finnish (FIN) AF: 0.440 AC: 4635 AN: 10540

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32331 AN: 67980

Other (OTH) AF: 0.455 AC: 959 AN: 2110

Alfa AF: 0.459 Hom.: 3348

Bravo AF: 0.454

Asia WGS AF: 0.641 AC: 2223 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.6
DANN	Benign	0.80
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

Publications

LitVar

Other links and lift over

dbSNP: rs4318528; hg19: chr3-56237417;