1-162790761-C-T

Variant names:

• chr1-162790761-C-T
• rs1704754
• NM_016371.4:c.-40C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016371.4. 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
	HSD17B7	NM_016371.4	MANE Select	c.-40C>T		5_prime_UTR	Exon 1 of 9	NP_057455.1
	HSD17B7	NM_001304512.2		c.-40C>T		5_prime_UTR	Exon 1 of 4	NP_001291441.1
	HSD17B7	NM_001304513.2		c.-40C>T		5_prime_UTR	Exon 1 of 4	NP_001291442.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B7	ENST00000254521.8	TSL:1 MANE Select	c.-40C>T		5_prime_UTR	Exon 1 of 9	ENSP00000254521.3
	HSD17B7	ENST00000963897.1		c.-40C>T		5_prime_UTR	Exon 1 of 9	ENSP00000633956.1
	HSD17B7	ENST00000902166.1		c.-40C>T		5_prime_UTR	Exon 1 of 9	ENSP00000572225.1

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

GnomAD2 exomes AF: 0.696 AC: 144211 AN: 207124 AF XY: 0.713

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 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

African (AFR) AF: 0.257 AC: 7154 AN: 27862

American (AMR) AF: 0.519 AC: 21127 AN: 40702

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 20253 AN: 23938

East Asian (EAS) AF: 0.550 AC: 20130 AN: 36568

South Asian (SAS) AF: 0.692 AC: 52626 AN: 76048

European-Finnish (FIN) AF: 0.829 AC: 42500 AN: 51292

Middle Eastern (MID) AF: 0.744 AC: 3852 AN: 5174

European-Non Finnish (NFE) AF: 0.802 AC: 677747 AN: 845016

Other (OTH) AF: 0.739 AC: 37078 AN: 50180

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

African (AFR) AF: 0.276 AC: 11344 AN: 41066

American (AMR) AF: 0.588 AC: 8910 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2944 AN: 3460

East Asian (EAS) AF: 0.575 AC: 2908 AN: 5056

South Asian (SAS) AF: 0.677 AC: 3218 AN: 4754

European-Finnish (FIN) AF: 0.832 AC: 8719 AN: 10480

Middle Eastern (MID) AF: 0.710 AC: 206 AN: 290

European-Non Finnish (NFE) AF: 0.797 AC: 54000 AN: 67762

Other (OTH) AF: 0.651 AC: 1362 AN: 2092

Alfa AF: 0.732 Hom.: 7821

Bravo AF: 0.587

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.53
DANN	Benign	0.91
PhyloP100		-2.0
PromoterAI		-0.099	Neutral
Mutation Taster		=300/0	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: rs1704754; hg19: chr1-162760551; COSMIC: COSV54418790; COSMIC: COSV54418790;