rs9875049

chr3-56423442-A-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ERC2	NM_015576.3	c.657+10909T>G		intron_variant		ENST00000288221.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERC2	ENST00000288221.11	c.657+10909T>G		intron_variant		1	NM_015576.3	P1
ERC2	ENST00000460849.5	c.657+10909T>G		intron_variant, NMD_transcript_variant		1
ERC2	ENST00000492584.3	c.657+10909T>G		intron_variant		5

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

Gnomad4 AFR AF: 0.0466

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.0297

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.0649

Gnomad4 FIN AF: 0.0558

Gnomad4 NFE AF: 0.0532

Gnomad4 OTH AF: 0.0678

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

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: rs9875049; hg19: chr3-56457470;