5-119489356-G-C

Position:

• chr5-119489356-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000414.4(HSD17B4):​c.714+73G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 895,662 control chromosomes in the GnomAD database, including 11,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (3314 hom., cov: 32)
  • Exomes 𝑓: 0.11 (7915 hom.)
• Consequence: HSD17B4 NM_000414.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-119489356-G-C is Benign according to our data. Variant chr5-119489356-G-C is described in ClinVar as [Benign]. Clinvar id is 1249115.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B4	NM_000414.4	c.714+73G>C		intron_variant		ENST00000510025.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B4	ENST00000510025.7	c.714+73G>C		intron_variant		2	NM_000414.4	P1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25465 AN: 151846 Hom.: 3305 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0897

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.113 AC: 84018 AN: 743698 Hom.: 7915 AF XY: 0.111 AC XY: 44191 AN XY: 397976

Gnomad4 AFR exome AF: 0.338

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.0846

Gnomad4 EAS exome AF: 0.452

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.0755

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.168 AC: 25497 AN: 151964 Hom.: 3314 Cov.: 32 AF XY: 0.170 AC XY: 12631 AN XY: 74270

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0897

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0765

Gnomad4 OTH AF: 0.122

Alfa AF: 0.126 Hom.: 219

Bravo AF: 0.177

Asia WGS AF: 0.230 AC: 799 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs12653702; hg19: chr5-118825051; COSMIC: COSV56333347; COSMIC: COSV56333347;