rs2231829

Variant names:

• chr20-45547937-G-A
• rs2231829
• ENST00000409554.1:c.-580C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-45547937-G-A
• chr20-45547937-G-T

Variant summary

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

The ENST00000409554.1(EPPIN):​c.-580C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 653,586 control chromosomes in the GnomAD database, including 362 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 0.035 (166 hom., cov: 31)
  • Exomes 𝑓: 0.020 (196 hom.)
• Consequence: EPPIN ENST00000409554.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

Genes affected

EPPIN (HGNC:15932): (epididymal peptidase inhibitor) This gene encodes an epididymal protease inhibitor, which contains both kunitz-type and WAP-type four-disulfide core (WFDC) protease inhibitor consensus sequences. Most WFDC genes are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene is a member of the WFDC gene family and belongs to the telomeric cluster. The protein can inhibit human sperm motility and exhibits antimicrobial activity against E. coli, and polymorphisms in this gene are associated with male infertility. Read-through transcription also exists between this gene and the downstream WFDC6 (WAP four-disulfide core domain 6) gene. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPPIN	ENST00000409554.1	c.-580C>T		upstream_gene_variant		5		ENSP00000387153.1

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5291 AN: 151640 Hom.: 168 Cov.: 31

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0495

Gnomad ASJ AF: 0.00952

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0289

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0341

GnomAD4 exome AF: 0.0198 AC: 9917 AN: 501828 Hom.: 196 AF XY: 0.0197 AC XY: 4653 AN XY: 235768

Gnomad4 AFR exome AF: 0.0442

Gnomad4 AMR exome AF: 0.0365

Gnomad4 ASJ exome AF: 0.00962

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.00549

Gnomad4 NFE exome AF: 0.0159

Gnomad4 OTH exome AF: 0.0370

GnomAD4 genome AF: 0.0349 AC: 5298 AN: 151758 Hom.: 166 Cov.: 31 AF XY: 0.0380 AC XY: 2819 AN XY: 74154

Gnomad4 AFR AF: 0.0403

Gnomad4 AMR AF: 0.0496

Gnomad4 ASJ AF: 0.00952

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.0289

Gnomad4 NFE AF: 0.0159

Gnomad4 OTH AF: 0.0343

Alfa AF: 0.0254 Hom.: 13

Bravo AF: 0.0357

Asia WGS AF: 0.156 AC: 542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.98
DANN	Benign	0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2231829; hg19: chr20-44176576;