20-45542073-C-A

Variant names:

• chr20-45542073-C-A
• rs11594
• ENST00000496898.1:n.3789G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000496898.1(EPPIN):​n.3789G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 1,584,742 control chromosomes in the GnomAD database, including 593,212 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 0.89 (60495 hom., cov: 32)
  • Exomes 𝑓: 0.86 (532717 hom.)
• Consequence: EPPIN ENST00000496898.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.03
• Publications: 18 publications found

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]

EPPIN-WFDC6 (HGNC:38825): (EPPIN-WFDC6 readthrough) This locus represents naturally occurring read-through transcription between the neighboring SPINLW1 (serine peptidase inhibitor-like, with Kunitz and WAP domains 1) and WFDC6 (WAP four-disulfide core domain 6) genes. The read-through transcript encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Nov 2010]

ENSG00000237464 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPPIN	NM_020398.4	c.*71G>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000354280.9	NP_065131.1
EPPIN	NM_001302861.2	c.*100G>T		3_prime_UTR_variant	Exon 4 of 4		NP_001289790.1
EPPIN-WFDC6	NM_001198986.2	c.391+627G>T		intron_variant	Intron 3 of 4		NP_001185915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPPIN	ENST00000354280.9	c.*71G>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_020398.4	ENSP00000361746.4
EPPIN-WFDC6	ENST00000651288.1	c.391+627G>T		intron_variant	Intron 3 of 4			ENSP00000498632.1

Frequencies

GnomAD3 genomes AF: 0.889 AC: 135297 AN: 152124 Hom.: 60425 Cov.: 32

Gnomad AFR AF: 0.974

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.880

GnomAD4 exome AF: 0.862 AC: 1234653 AN: 1432500 Hom.: 532717 Cov.: 24 AF XY: 0.861 AC XY: 612161 AN XY: 711004

African (AFR) AF: 0.979 AC: 31823 AN: 32508

American (AMR) AF: 0.897 AC: 36522 AN: 40726

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 18624 AN: 25002

East Asian (EAS) AF: 0.909 AC: 35626 AN: 39196

South Asian (SAS) AF: 0.868 AC: 71489 AN: 82320

European-Finnish (FIN) AF: 0.848 AC: 44828 AN: 52886

Middle Eastern (MID) AF: 0.848 AC: 4772 AN: 5628

European-Non Finnish (NFE) AF: 0.859 AC: 940335 AN: 1095126

Other (OTH) AF: 0.857 AC: 50634 AN: 59108

GnomAD4 genome AF: 0.890 AC: 135426 AN: 152242 Hom.: 60495 Cov.: 32 AF XY: 0.889 AC XY: 66127 AN XY: 74422

African (AFR) AF: 0.974 AC: 40468 AN: 41552

American (AMR) AF: 0.892 AC: 13647 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2621 AN: 3470

East Asian (EAS) AF: 0.898 AC: 4647 AN: 5176

South Asian (SAS) AF: 0.865 AC: 4180 AN: 4832

European-Finnish (FIN) AF: 0.849 AC: 8989 AN: 10592

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.852 AC: 57921 AN: 68002

Other (OTH) AF: 0.878 AC: 1857 AN: 2114

Alfa AF: 0.872 Hom.: 96949

Bravo AF: 0.896

Asia WGS AF: 0.883 AC: 3069 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.020
DANN	Benign	0.63
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11594; hg19: chr20-44170712;