5-119489356-G-C

Variant names:

• chr5-119489356-G-C
• rs12653702
• NM_000414.4:c.714+73G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

HSD17B4 Gene-Disease associations (from GenCC):

• d-bifunctional protein deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Perrault syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Perrault syndrome 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000414.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B4	NM_000414.4	MANE Select	c.714+73G>C		intron	N/A	NP_000405.1
	HSD17B4	NM_001199291.3		c.789+73G>C		intron	N/A	NP_001186220.1
	HSD17B4	NM_001374497.1		c.705+73G>C		intron	N/A	NP_001361426.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B4	ENST00000510025.7	TSL:2 MANE Select	c.714+73G>C		intron	N/A	ENSP00000424940.3
	HSD17B4	ENST00000509514.6	TSL:1	c.714+73G>C		intron	N/A	ENSP00000426272.2
	HSD17B4	ENST00000414835.7	TSL:2	c.789+73G>C		intron	N/A	ENSP00000411960.3

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

African (AFR) AF: 0.338 AC: 6568 AN: 19406

American (AMR) AF: 0.111 AC: 4759 AN: 42880

Ashkenazi Jewish (ASJ) AF: 0.0846 AC: 1819 AN: 21496

East Asian (EAS) AF: 0.452 AC: 16310 AN: 36112

South Asian (SAS) AF: 0.123 AC: 8730 AN: 70822

European-Finnish (FIN) AF: 0.120 AC: 6300 AN: 52524

Middle Eastern (MID) AF: 0.102 AC: 447 AN: 4368

European-Non Finnish (NFE) AF: 0.0755 AC: 34695 AN: 459662

Other (OTH) AF: 0.121 AC: 4390 AN: 36428

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

African (AFR) AF: 0.342 AC: 14142 AN: 41410

American (AMR) AF: 0.103 AC: 1578 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0897 AC: 311 AN: 3468

East Asian (EAS) AF: 0.410 AC: 2109 AN: 5142

South Asian (SAS) AF: 0.131 AC: 631 AN: 4816

European-Finnish (FIN) AF: 0.113 AC: 1190 AN: 10554

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0765 AC: 5204 AN: 67986

Other (OTH) AF: 0.122 AC: 258 AN: 2110

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

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.66
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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