rs1795648

chr3-55537732-G-Achr3-55537732-G-Cchr3-55537732-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015576.3(ERC2):c.*40-26456C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 152,094 control chromosomes in the GnomAD database, including 33,675 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 0.65 (33675 hom., cov: 33)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.685

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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERC2	NM_015576.3	c.*40-26456C>T		intron_variant		ENST00000288221.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERC2	ENST00000288221.11	c.*40-26456C>T		intron_variant		1	NM_015576.3	P1

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98909 AN: 151976 Hom.: 33659 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.681

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

GnomAD4 genome AF: 0.651 AC: 98975 AN: 152094 Hom.: 33675 Cov.: 33 AF XY: 0.657 AC XY: 48865 AN XY: 74354

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.786

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.680

Alfa AF: 0.721 Hom.: 84553

Bravo AF: 0.632

Asia WGS AF: 0.754 AC: 2619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	9.1
Dann	Benign	0.82

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: rs1795648; hg19: chr3-55571760;