rs11594

Positions:

• chr20-45542073-C-A
• chr20-45542073-C-G
• chr20-45542073-C-T

Variant summary

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

The NM_020398.4(EPPIN):​c.*71G>T variant causes a 3 prime UTR 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 NM_020398.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.03

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
EPPIN	NM_020398.4	c.*71G>T		3_prime_UTR_variant	4/4	ENST00000354280.9
EPPIN-WFDC6	NM_001198986.2	c.391+627G>T		intron_variant
EPPIN	NM_001302861.2	c.*100G>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPPIN	ENST00000354280.9	c.*71G>T		3_prime_UTR_variant	4/4	1	NM_020398.4	P1
EPPIN	ENST00000336443.3	c.*71G>T		3_prime_UTR_variant	3/3	1
EPPIN	ENST00000496898.1	n.3789G>T		non_coding_transcript_exon_variant	2/2	1
EPPIN	ENST00000409554.1	c.*129G>T		3_prime_UTR_variant	4/4	5

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

Gnomad4 AFR exome AF: 0.979

Gnomad4 AMR exome AF: 0.897

Gnomad4 ASJ exome AF: 0.745

Gnomad4 EAS exome AF: 0.909

Gnomad4 SAS exome AF: 0.868

Gnomad4 FIN exome AF: 0.848

Gnomad4 NFE exome AF: 0.859

Gnomad4 OTH exome AF: 0.857

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

Gnomad4 AFR AF: 0.974

Gnomad4 AMR AF: 0.892

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.849

Gnomad4 NFE AF: 0.852

Gnomad4 OTH AF: 0.878

Alfa AF: 0.856 Hom.: 53643

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

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: rs11594; hg19: chr20-44170712;