rs1412049334

Variant names:

• chr1-162792847-A-G
• rs1412049334
• NM_016371.4:c.224A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016371.4(HSD17B7):​c.224A>G​(p.Lys75Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSD17B7 NM_016371.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.559
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050706536).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B7	NM_016371.4	MANE Select	c.224A>G	p.Lys75Arg	missense	Exon 2 of 9	NP_057455.1	P56937-1
	HSD17B7	NM_001304512.2		c.224A>G	p.Lys75Arg	missense	Exon 2 of 4	NP_001291441.1
	HSD17B7	NM_001304513.2		c.224A>G	p.Lys75Arg	missense	Exon 2 of 4	NP_001291442.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B7	ENST00000254521.8	TSL:1 MANE Select	c.224A>G	p.Lys75Arg	missense	Exon 2 of 9	ENSP00000254521.3	P56937-1
	HSD17B7	ENST00000902168.1		c.224A>G	p.Lys75Arg	missense	Exon 2 of 9	ENSP00000572227.1
	HSD17B7	ENST00000963897.1		c.224A>G	p.Lys75Arg	missense	Exon 2 of 9	ENSP00000633956.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251462 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000274 AC: 4 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	1.5
DANN	Benign	0.58
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.020	N
PhyloP100		0.56
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.097
Sift	Benign	0.23	T
Sift4G	Benign	0.36	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.37		Loss of ubiquitination at K75 (P = 0.0446)
MVP		0.63
MPC		0.39
ClinPred		0.041	T
GERP RS		-5.1
Varity_R		0.048
gMVP		0.25
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1412049334; hg19: chr1-162762637;