rs11719646

chr3-56433663-A-G

Variant summary

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

The NM_015576.3(ERC2):c.657+688T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,344 control chromosomes in the GnomAD database, including 9,834 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 0.36 (9830 hom., cov: 33)
  • Exomes 𝑓: 0.24 (4 hom.)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERC2	NM_015576.3	c.657+688T>C		intron_variant		ENST00000288221.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERC2	ENST00000288221.11	c.657+688T>C		intron_variant		1	NM_015576.3	P1
ERC2	ENST00000460849.5	c.657+688T>C		intron_variant, NMD_transcript_variant		1
ERC2	ENST00000492584.3	c.657+688T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54101 AN: 152044 Hom.: 9822 Cov.: 33

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.242 AC: 44 AN: 182 Hom.: 4 AF XY: 0.198 AC XY: 21 AN XY: 106

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.143

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.356 AC: 54133 AN: 152162 Hom.: 9830 Cov.: 33 AF XY: 0.349 AC XY: 25990 AN XY: 74396

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.375

Alfa AF: 0.369 Hom.: 22106

Bravo AF: 0.351

Asia WGS AF: 0.222 AC: 773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.3
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11719646; hg19: chr3-56467691;