NM_178135.5:c.451-8T>G

Variant names:

• chr4-87315607-A-C
• rs201689424
• NM_178135.5:c.451-8T>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PP3 BP6_Very_Strong BS2

The NM_178135.5(HSD17B13):​c.451-8T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000368 in 1,544,134 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: HSD17B13 NM_178135.5 splice_region, intron
• Scores: Splicing: ADA: 0.9619
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.59
• Publications: 0 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: Benign. The variant received -11 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 4-87315607-A-C is Benign according to our data. Variant chr4-87315607-A-C is described in ClinVar as [Benign]. Clinvar id is 775996.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B13	NM_178135.5	c.451-8T>G		splice_region_variant, intron_variant	Intron 3 of 6	ENST00000328546.5	NP_835236.2
HSD17B13	NM_001136230.3	c.343-8T>G		splice_region_variant, intron_variant	Intron 2 of 5		NP_001129702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B13	ENST00000328546.5	c.451-8T>G		splice_region_variant, intron_variant	Intron 3 of 6	1	NM_178135.5	ENSP00000333300.4
HSD17B13	ENST00000302219.10	c.343-8T>G		splice_region_variant, intron_variant	Intron 2 of 5	1		ENSP00000305438.6

Frequencies

GnomAD3 genomes AF: 0.00217 AC: 330 AN: 152216 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00745

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000513 AC: 124 AN: 241918 AF XY: 0.000428

Gnomad AFR exome AF: 0.00682

Gnomad AMR exome AF: 0.000410

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000900

Gnomad OTH exome AF: 0.000170

GnomAD4 exome AF: 0.000172 AC: 239 AN: 1391800 Hom.: 0 Cov.: 21 AF XY: 0.000139 AC XY: 96 AN XY: 691884

African (AFR) AF: 0.00589 AC: 188 AN: 31928

American (AMR) AF: 0.000405 AC: 17 AN: 42000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25286

East Asian (EAS) AF: 0.00 AC: 0 AN: 38882

South Asian (SAS) AF: 0.00 AC: 0 AN: 82728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52886

Middle Eastern (MID) AF: 0.000357 AC: 2 AN: 5598

European-Non Finnish (NFE) AF: 0.0000114 AC: 12 AN: 1054830

Other (OTH) AF: 0.000347 AC: 20 AN: 57662

GnomAD4 genome AF: 0.00216 AC: 329 AN: 152334 Hom.: 2 Cov.: 32 AF XY: 0.00235 AC XY: 175 AN XY: 74490

African (AFR) AF: 0.00741 AC: 308 AN: 41576

American (AMR) AF: 0.00118 AC: 18 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000774 Hom.: 0

Bravo AF: 0.00231

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	20
DANN	Benign	0.70
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.96
dbscSNV1_RF	Pathogenic	0.90
SpliceAI score (max)		0.94		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.94		Position offset: -1
DS_AL_spliceai		0.35		Position offset: -8

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

Other links and lift over

dbSNP: rs201689424; hg19: chr4-88236759;