rs2227290

Variant names:

• chr20-45547503-G-C
• rs2227290
• ENST00000651288.1:c.-146C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-45547503-G-C
• chr20-45547503-G-T

Variant summary

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

The ENST00000651288.1(EPPIN-WFDC6):​c.-146C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000541 in 1,477,380 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: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000053 (0 hom.)
• Consequence: EPPIN-WFDC6 ENST00000651288.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166
• Publications: 5 publications found

Genes affected

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]

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]

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=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPPIN	NM_020398.4	c.-146C>G		upstream_gene_variant		ENST00000354280.9	NP_065131.1
EPPIN-WFDC6	NM_001198986.2	c.-146C>G		upstream_gene_variant			NP_001185915.1
EPPIN	NM_001302861.2	c.-146C>G		upstream_gene_variant			NP_001289790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPPIN-WFDC6	ENST00000651288.1	c.-146C>G		5_prime_UTR_variant	Exon 1 of 5			ENSP00000498632.1
EPPIN	ENST00000354280.9	c.-146C>G		upstream_gene_variant		1	NM_020398.4	ENSP00000361746.4

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151856 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000528 AC: 7 AN: 1325524 Hom.: 0 Cov.: 29 AF XY: 0.00000771 AC XY: 5 AN XY: 648428

African (AFR) AF: 0.00 AC: 0 AN: 29680

American (AMR) AF: 0.00 AC: 0 AN: 28460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20854

East Asian (EAS) AF: 0.000198 AC: 7 AN: 35410

South Asian (SAS) AF: 0.00 AC: 0 AN: 67352

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1052282

Other (OTH) AF: 0.00 AC: 0 AN: 55242

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151856 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74118

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

African (AFR) AF: 0.00 AC: 0 AN: 41372

American (AMR) AF: 0.00 AC: 0 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67944

Other (OTH) AF: 0.00 AC: 0 AN: 2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 1335

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.60
PhyloP100		0.17
PromoterAI		0.037	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2227290; hg19: chr20-44176142;