20-45542073-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000496898.1(EPPIN):​n.3789G>A 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 0.0000014 in 1,433,416 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPPIN	NM_020398.4	c.*71G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000354280.9	NP_065131.1
EPPIN	NM_001302861.2	c.*100G>A		3_prime_UTR_variant	Exon 4 of 4		NP_001289790.1
EPPIN-WFDC6	NM_001198986.2	c.391+627G>A		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>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_020398.4	ENSP00000361746.4
EPPIN-WFDC6	ENST00000651288.1	c.391+627G>A		intron_variant	Intron 3 of 4			ENSP00000498632.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1433416 Hom.: 0 Cov.: 24 AF XY: 0.00000281 AC XY: 2 AN XY: 711478

African (AFR) AF: 0.00 AC: 0 AN: 32520

American (AMR) AF: 0.0000245 AC: 1 AN: 40754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39202

South Asian (SAS) AF: 0.00 AC: 0 AN: 82412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52914

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5632

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095800

Other (OTH) AF: 0.00 AC: 0 AN: 59158

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 96949

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.034
DANN	Benign	0.91
PhyloP100		-3.0

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

Other links and lift over

dbSNP: rs11594; hg19: chr20-44170712;