chr4-87310240-T-TA

Variant names:

• chr4-87310240-T-TA
• rs72613567
• NM_178135.5:c.812+2dupT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 4P and 10B. PVS1_Strong BP6_Moderate BA1

The NM_178135.5(HSD17B13):​c.812+2dupT variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.25 in 1,559,610 control chromosomes in the GnomAD database, including 52,195 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3546 hom., cov: 25)
  • Exomes 𝑓: 0.26 (48649 hom.)
• Consequence: HSD17B13 NM_178135.5 splice_donor, intron
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 3.85
• Publications: 285 publications found

Genes affected

HSD17B13 (HGNC:18685): (hydroxysteroid 17-beta dehydrogenase 13) Predicted to enable oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor and steroid dehydrogenase activity. Acts upstream of or within positive regulation of lipid biosynthetic process. Located in lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.1295681 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• BP6: Variant 4-87310240-T-TA is Benign according to our data. Variant chr4-87310240-T-TA is described in ClinVar as [Benign]. Clinvar id is 1247925.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B13	NM_178135.5	c.812+2dupT		splice_donor_variant, intron_variant	Intron 6 of 6	ENST00000328546.5	NP_835236.2
HSD17B13	NM_001136230.3	c.704+2dupT		splice_donor_variant, intron_variant	Intron 5 of 5		NP_001129702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B13	ENST00000328546.5	c.812+2dupT		splice_donor_variant, intron_variant	Intron 6 of 6	1	NM_178135.5	ENSP00000333300.4
HSD17B13	ENST00000302219.10	c.704+2dupT		splice_donor_variant, intron_variant	Intron 5 of 5	1		ENSP00000305438.6

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29900 AN: 151682 Hom.: 3550 Cov.: 25

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.193

GnomAD2 exomes AF: 0.218 AC: 42845 AN: 196970 AF XY: 0.221

Gnomad AFR exome AF: 0.0590

Gnomad AMR exome AF: 0.0945

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.323

Gnomad FIN exome AF: 0.209

Gnomad NFE exome AF: 0.268

Gnomad OTH exome AF: 0.215

GnomAD4 exome AF: 0.256 AC: 360076 AN: 1407814 Hom.: 48649 Cov.: 34 AF XY: 0.253 AC XY: 177130 AN XY: 700012

African (AFR) AF: 0.0603 AC: 1773 AN: 29384

American (AMR) AF: 0.107 AC: 3234 AN: 30194

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 5583 AN: 24178

East Asian (EAS) AF: 0.327 AC: 11987 AN: 36706

South Asian (SAS) AF: 0.154 AC: 11937 AN: 77436

European-Finnish (FIN) AF: 0.213 AC: 11273 AN: 52858

Middle Eastern (MID) AF: 0.182 AC: 1019 AN: 5584

European-Non Finnish (NFE) AF: 0.274 AC: 299771 AN: 1093450

Other (OTH) AF: 0.233 AC: 13499 AN: 58024

GnomAD4 genome AF: 0.197 AC: 29887 AN: 151796 Hom.: 3546 Cov.: 25 AF XY: 0.193 AC XY: 14311 AN XY: 74182

African (AFR) AF: 0.0690 AC: 2863 AN: 41488

American (AMR) AF: 0.168 AC: 2557 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 766 AN: 3462

East Asian (EAS) AF: 0.341 AC: 1758 AN: 5156

South Asian (SAS) AF: 0.169 AC: 812 AN: 4806

European-Finnish (FIN) AF: 0.208 AC: 2169 AN: 10420

Middle Eastern (MID) AF: 0.193 AC: 56 AN: 290

European-Non Finnish (NFE) AF: 0.269 AC: 18267 AN: 67908

Other (OTH) AF: 0.192 AC: 405 AN: 2104

Alfa AF: 0.224 Hom.: 870

Bravo AF: 0.189

Asia WGS AF: 0.232 AC: 808 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 32161197, 32039348, 30415504, 30908678, 29562163) -

FATTY LIVER DISEASE, PROTECTION AGAINST Benign:1

Apr 23, 2025

OMIM

Significance: protective

Review Status: no assertion criteria provided

Collection Method: literature only

- -

HSD17B13 POLYMORPHISM Benign:1

Apr 23, 2025

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9
Mutation Taster		=89/11	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs72613567; hg19: chr4-88231392; COSMIC: COSV105876830;