5-119527276-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000414.4(HSD17B4):c.1767+57C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 974,272 control chromosomes in the GnomAD database, including 176,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (30167 hom., cov: 31)
  • Exomes 𝑓: 0.59 (146638 hom.)
• Consequence: HSD17B4 NM_000414.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.742

Genes affected

HSD17B4 (HGNC:5213): (hydroxysteroid 17-beta dehydrogenase 4) The protein encoded by this gene is a bifunctional enzyme that is involved in the peroxisomal beta-oxidation pathway for fatty acids. It also acts as a catalyst for the formation of 3-ketoacyl-CoA intermediates from both straight-chain and 2-methyl-branched-chain fatty acids. Defects in this gene that affect the peroxisomal fatty acid beta-oxidation activity are a cause of D-bifunctional protein deficiency (DBPD). An apparent pseudogene of this gene is present on chromosome 8. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-119527276-C-T is Benign according to our data. Variant chr5-119527276-C-T is described in ClinVar as [Benign]. Clinvar id is 1185150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B4	NM_000414.4	c.1767+57C>T		intron_variant		ENST00000510025.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B4	ENST00000510025.7	c.1767+57C>T		intron_variant		2	NM_000414.4	P1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94681 AN: 151602 Hom.: 30138 Cov.: 31

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.617

GnomAD4 exome AF: 0.586 AC: 481715 AN: 822552 Hom.: 146638 AF XY: 0.582 AC XY: 252534 AN XY: 434142

Gnomad4 AFR exome AF: 0.693

Gnomad4 AMR exome AF: 0.687

Gnomad4 ASJ exome AF: 0.632

Gnomad4 EAS exome AF: 0.936

Gnomad4 SAS exome AF: 0.539

Gnomad4 FIN exome AF: 0.643

Gnomad4 NFE exome AF: 0.548

Gnomad4 OTH exome AF: 0.592

GnomAD4 genome AF: 0.625 AC: 94763 AN: 151720 Hom.: 30167 Cov.: 31 AF XY: 0.629 AC XY: 46627 AN XY: 74128

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.923

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.613

Alfa AF: 0.604 Hom.: 4086

Bravo AF: 0.632

Asia WGS AF: 0.713 AC: 2463 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Bifunctional peroxisomal enzyme deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Perrault syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.23
Dann	Benign	0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2636961; hg19: chr5-118862971; COSMIC: COSV56333355; COSMIC: COSV56333355;