chr3-56006952-G-C

Variant names:

• chr3-56006952-G-C
• rs1379716
• NM_015576.3:c.2061+229C>G

Variant summary

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

The NM_015576.3(ERC2):​c.2061+229C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 152,118 control chromosomes in the GnomAD database, including 67,618 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 0.94 (67618 hom., cov: 32)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395
• Publications: 0 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERC2	NM_015576.3	c.2061+229C>G		intron_variant	Intron 10 of 17	ENST00000288221.11	NP_056391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERC2	ENST00000288221.11	c.2061+229C>G		intron_variant	Intron 10 of 17	1	NM_015576.3	ENSP00000288221.6
ERC2	ENST00000460849.5	n.2061+229C>G		intron_variant	Intron 10 of 18	1		ENSP00000417445.1
ERC2	ENST00000492584.3	c.2061+229C>G		intron_variant	Intron 10 of 17	5		ENSP00000417280.3

Frequencies

GnomAD3 genomes AF: 0.941 AC: 143069 AN: 152000 Hom.: 67566 Cov.: 32

Gnomad AFR AF: 0.850

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.995

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.974

Gnomad OTH AF: 0.952

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

GnomAD4 genome AF: 0.941 AC: 143178 AN: 152118 Hom.: 67618 Cov.: 32 AF XY: 0.943 AC XY: 70137 AN XY: 74380

African (AFR) AF: 0.850 AC: 35268 AN: 41496

American (AMR) AF: 0.974 AC: 14851 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 3431 AN: 3468

East Asian (EAS) AF: 1.00 AC: 5178 AN: 5178

South Asian (SAS) AF: 0.996 AC: 4804 AN: 4824

European-Finnish (FIN) AF: 0.966 AC: 10248 AN: 10608

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.974 AC: 66181 AN: 67972

Other (OTH) AF: 0.953 AC: 2014 AN: 2114

Alfa AF: 0.963 Hom.: 3334

Bravo AF: 0.936

Asia WGS AF: 0.990 AC: 3427 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.8
DANN	Benign	0.60
PhyloP100		-0.40
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: rs1379716; hg19: chr3-56040980;