rs4318528

Positions:

• chr3-56203389-G-A
• chr3-56203389-G-C
• chr3-56203389-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.1075-29869C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,998 control chromosomes in the GnomAD database, including 16,243 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 0.46 (16243 hom., cov: 33)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.459

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERC2	NM_015576.3	c.1075-29869C>T		intron_variant		ENST00000288221.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERC2	ENST00000288221.11	c.1075-29869C>T		intron_variant		1	NM_015576.3	P1
ERC2	ENST00000460849.5	c.1075-29869C>T		intron_variant, NMD_transcript_variant		1
ERC2	ENST00000492584.3	c.1075-29869C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69163 AN: 151880 Hom.: 16238 Cov.: 33

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.455 AC: 69203 AN: 151998 Hom.: 16243 Cov.: 33 AF XY: 0.459 AC XY: 34097 AN XY: 74294

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.455

Alfa AF: 0.462 Hom.: 3306

Bravo AF: 0.454

Asia WGS AF: 0.641 AC: 2223 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.6
DANN	Benign	0.80

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: rs4318528; hg19: chr3-56237417;