chr3-56423442-A-C

Variant names:

• chr3-56423442-A-C
• rs9875049
• NM_015576.3:c.657+10909T>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.657+10909T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.065 in 152,308 control chromosomes in the GnomAD database, including 494 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 0.065 (494 hom., cov: 32)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERC2	NM_015576.3	c.657+10909T>G		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+10909T>G		intron_variant	Intron 2 of 17	1	NM_015576.3	ENSP00000288221.6
ERC2	ENST00000460849.5	n.657+10909T>G		intron_variant	Intron 2 of 18	1		ENSP00000417445.1
ERC2	ENST00000492584.3	c.657+10909T>G		intron_variant	Intron 2 of 17	5		ENSP00000417280.3

Frequencies

GnomAD3 genomes AF: 0.0649 AC: 9883 AN: 152190 Hom.: 488 Cov.: 32

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0646

Gnomad FIN AF: 0.0558

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0533

Gnomad OTH AF: 0.0690

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

GnomAD4 genome AF: 0.0650 AC: 9898 AN: 152308 Hom.: 494 Cov.: 32 AF XY: 0.0665 AC XY: 4955 AN XY: 74484

African (AFR) AF: 0.0466 AC: 1939 AN: 41584

American (AMR) AF: 0.158 AC: 2419 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0297 AC: 103 AN: 3470

East Asian (EAS) AF: 0.142 AC: 736 AN: 5174

South Asian (SAS) AF: 0.0649 AC: 313 AN: 4822

European-Finnish (FIN) AF: 0.0558 AC: 592 AN: 10618

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0532 AC: 3621 AN: 68024

Other (OTH) AF: 0.0678 AC: 143 AN: 2110

Alfa AF: 0.0672 Hom.: 124

Bravo AF: 0.0716

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.67
PhyloP100		-0.25
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: rs9875049; hg19: chr3-56457470;