rs7644975

Variant names:

• chr3-56371141-G-A
• rs7644975
• NM_015576.3:c.657+63210C>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.657+63210C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,076 control chromosomes in the GnomAD database, including 4,660 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 0.23 (4660 hom., cov: 32)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERC2	NM_015576.3	c.657+63210C>T		intron_variant	Intron 2 of 17	ENST00000288221.11	NP_056391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERC2	ENST00000288221.11	c.657+63210C>T		intron_variant	Intron 2 of 17	1	NM_015576.3	ENSP00000288221.6
ERC2	ENST00000460849.5	n.657+63210C>T		intron_variant	Intron 2 of 18	1		ENSP00000417445.1
ERC2	ENST00000492584.3	c.657+63210C>T		intron_variant	Intron 2 of 17	5		ENSP00000417280.3

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35191 AN: 151960 Hom.: 4652 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.232 AC: 35216 AN: 152076 Hom.: 4660 Cov.: 32 AF XY: 0.233 AC XY: 17324 AN XY: 74350

African (AFR) AF: 0.109 AC: 4522 AN: 41498

American (AMR) AF: 0.282 AC: 4309 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3468

East Asian (EAS) AF: 0.133 AC: 689 AN: 5168

South Asian (SAS) AF: 0.173 AC: 834 AN: 4810

European-Finnish (FIN) AF: 0.326 AC: 3441 AN: 10556

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19878 AN: 67980

Other (OTH) AF: 0.222 AC: 469 AN: 2116

Alfa AF: 0.246 Hom.: 970

Bravo AF: 0.223

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.69
PhyloP100		-0.059
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: rs7644975; hg19: chr3-56405169;