Genetic Variant ENSG00000237464:n.519+7660G>A (chr20-45547937-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0900

Publications

7 publications found

Variant links:

Genes affected

ENSG00000237464 (HGNC:):

ENSG00000237464 links:

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 links:

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ACMG classification

Classification was made for transcript

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 link	n.519+7660G>A		intron_variant	Intron 4 of 4
EPPIN	ENST00000409554.1 link	c.-580C>T		upstream_gene_variant		5		ENSP00000387153.1		B7ZBA9

Frequencies

GnomAD3 genomes

AF:

0.0349

AC:

5291

AN:

151640

Hom.:

168

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0442

AC:

410

AN:

9280

American (AMR)

AF:

0.0365

AC:

AN:

548

Ashkenazi Jewish (ASJ)

AF:

0.00962

AC:

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:

AN:

182

Middle Eastern (MID)

AF:

0.0399

AC:

AN:

1002

European-Non Finnish (NFE)

AF:

0.0159

AC:

7316

AN:

459220

Other (OTH)

AF:

0.0370

AC:

608

AN:

16426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

455

910

1366

1821

2276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

434

868

1302

1736

2170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0349

AC:

5298

AN:

151758

Hom.:

166

Cov.:

AF XY:

0.0380

AC XY:

2819

AN XY:

74154

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0159

AC:

1083

AN:

67962

Other (OTH)

AF:

0.0343

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

241

481

722

962

1203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0254

Hom.:

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

(source)

DANN

Benign

0.47

PhyloP100

-0.090

PromoterAI

-0.0094

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over