rs2231829

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-45547937-G-A
• chr20-45547937-G-T

Variant summary

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

The ENST00000803561.1(ENSG00000237464):​n.519+7660G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 653,586 control chromosomes in the GnomAD database, including 362 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 0.035 (166 hom., cov: 31)
  • Exomes 𝑓: 0.020 (196 hom.)
• Consequence: ENSG00000237464 ENST00000803561.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

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>A		intron_variant	Intron 4 of 4
EPPIN	ENST00000409554.1	c.-580C>T		upstream_gene_variant		5		ENSP00000387153.1

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5291 AN: 151640 Hom.: 168 Cov.: 31

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0495

Gnomad ASJ AF: 0.00952

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0289

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0341

GnomAD4 exome AF: 0.0198 AC: 9917 AN: 501828 Hom.: 196 AF XY: 0.0197 AC XY: 4653 AN XY: 235768

African (AFR) AF: 0.0442 AC: 410 AN: 9280

American (AMR) AF: 0.0365 AC: 20 AN: 548

Ashkenazi Jewish (ASJ) AF: 0.00962 AC: 30 AN: 3120

East Asian (EAS) AF: 0.162 AC: 353 AN: 2184

South Asian (SAS) AF: 0.115 AC: 1139 AN: 9866

European-Finnish (FIN) AF: 0.00549 AC: 1 AN: 182

Middle Eastern (MID) AF: 0.0399 AC: 40 AN: 1002

European-Non Finnish (NFE) AF: 0.0159 AC: 7316 AN: 459220

Other (OTH) AF: 0.0370 AC: 608 AN: 16426

GnomAD4 genome AF: 0.0349 AC: 5298 AN: 151758 Hom.: 166 Cov.: 31 AF XY: 0.0380 AC XY: 2819 AN XY: 74154

African (AFR) AF: 0.0403 AC: 1667 AN: 41346

American (AMR) AF: 0.0496 AC: 757 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00952 AC: 33 AN: 3468

East Asian (EAS) AF: 0.167 AC: 855 AN: 5128

South Asian (SAS) AF: 0.108 AC: 520 AN: 4806

European-Finnish (FIN) AF: 0.0289 AC: 303 AN: 10488

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0159 AC: 1083 AN: 67962

Other (OTH) AF: 0.0343 AC: 72 AN: 2102

Alfa AF: 0.0254 Hom.: 13

Bravo AF: 0.0357

Asia WGS AF: 0.156 AC: 542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.98
DANN	Benign	0.47
PhyloP100		-0.090
PromoterAI		-0.0094	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;