1-162790761-C-T

Position:

• chr1-162790761-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016371.4(HSD17B7):​c.-40C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,034 control chromosomes in the GnomAD database, including 33,370 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.62 (33370 hom., cov: 26)
  • Exomes 𝑓: 0.76 (343531 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSD17B7 NM_016371.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

Genes affected

HSD17B7 (HGNC:5215): (hydroxysteroid 17-beta dehydrogenase 7) HSD17B7 encodes an enzyme that functions both as a 17-beta-hydroxysteroid dehydrogenase (EC 1.1.1.62) in the biosynthesis of sex steroids and as a 3-ketosteroid reductase (EC 1.1.1.270) in the biosynthesis of cholesterol (Marijanovic et al., 2003 [PubMed 12829805]).[supplied by OMIM, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B7	NM_016371.4	c.-40C>T		5_prime_UTR_variant	1/9	ENST00000254521.8
HSD17B7	NM_001304512.2	c.-40C>T		5_prime_UTR_variant	1/4
HSD17B7	NM_001304513.2	c.-40C>T		5_prime_UTR_variant	1/4
HSD17B7	XR_007060779.1	n.60C>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B7	ENST00000254521.8	c.-40C>T		5_prime_UTR_variant	1/9	1	NM_016371.4	P1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94230 AN: 150922 Hom.: 33368 Cov.: 26

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.651

GnomAD3 exomes AF: 0.696 AC: 144211 AN: 207124 Hom.: 52919 AF XY: 0.713 AC XY: 79399 AN XY: 111344

Gnomad AFR exome AF: 0.257

Gnomad AMR exome AF: 0.508

Gnomad ASJ exome AF: 0.848

Gnomad EAS exome AF: 0.590

Gnomad SAS exome AF: 0.685

Gnomad FIN exome AF: 0.831

Gnomad NFE exome AF: 0.798

Gnomad OTH exome AF: 0.743

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.763 AC: 882467 AN: 1156780 Hom.: 343531 Cov.: 16 AF XY: 0.764 AC XY: 448106 AN XY: 586166

Gnomad4 AFR exome AF: 0.257

Gnomad4 AMR exome AF: 0.519

Gnomad4 ASJ exome AF: 0.846

Gnomad4 EAS exome AF: 0.550

Gnomad4 SAS exome AF: 0.692

Gnomad4 FIN exome AF: 0.829

Gnomad4 NFE exome AF: 0.802

Gnomad4 OTH exome AF: 0.739

GnomAD4 genome AF: 0.624 AC: 94240 AN: 151034 Hom.: 33370 Cov.: 26 AF XY: 0.625 AC XY: 46073 AN XY: 73770

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.851

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.651

Alfa AF: 0.732 Hom.: 7821

Bravo AF: 0.587

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.53
DANN	Benign	0.91

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: rs1704754; hg19: chr1-162760551; COSMIC: COSV54418790; COSMIC: COSV54418790;