chr20-45547937-G-T

Variant names:

• chr20-45547937-G-T
• rs2231829
• ENST00000803561.1:n.519+7660G>T

Variant summary

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

The ENST00000803561.1(ENSG00000237464):​n.519+7660G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000398 in 501,982 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: 31)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: ENSG00000237464 ENST00000803561.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• Publications: 0 publications found

Genes affected

ENSG00000237464 (HGNC:):

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

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000237464	ENST00000803561.1	n.519+7660G>T		intron_variant	Intron 4 of 4
EPPIN	ENST00000409554.1	c.-580C>A		upstream_gene_variant		5		ENSP00000387153.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000398 AC: 2 AN: 501982 Hom.: 0 AF XY: 0.00000424 AC XY: 1 AN XY: 235844

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 9290

American (AMR) AF: 0.00 AC: 0 AN: 548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3120

East Asian (EAS) AF: 0.00 AC: 0 AN: 2184

South Asian (SAS) AF: 0.00 AC: 0 AN: 9884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1004

European-Non Finnish (NFE) AF: 0.00000435 AC: 2 AN: 459332

Other (OTH) AF: 0.00 AC: 0 AN: 16438

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.40
DANN	Benign	0.45
PhyloP100		-0.090
PromoterAI		0.00090	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2231829; hg19: chr20-44176576;