rs17849880

Variant names:

• chr16-30987877-C-T
• rs17849880
• NM_025193.4:c.804C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The ENST00000297679.10(HSD3B7):​c.804C>T​(p.Tyr268Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.094 in 1,613,850 control chromosomes in the GnomAD database, including 8,129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (480 hom., cov: 34)
  • Exomes 𝑓: 0.097 (7649 hom.)
• Consequence: HSD3B7 ENST00000297679.10 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0240
• Publications: 14 publications found

Genes affected

HSD3B7 (HGNC:18324): (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7) This gene encodes an enzyme which is involved in the initial stages of the synthesis of bile acids from cholesterol and a member of the short-chain dehydrogenase/reductase superfamily. The encoded protein is a membrane-associated endoplasmic reticulum protein which is active against 7-alpha hydrosylated sterol substrates. Mutations in this gene are associated with a congenital bile acid synthesis defect which leads to neonatal cholestasis, a form of progressive liver disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

HSD3B7 Gene-Disease associations (from GenCC):

• congenital bile acid synthesis defect 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000279196 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 16-30987877-C-T is Benign according to our data. Variant chr16-30987877-C-T is described in ClinVar as Benign. ClinVar VariationId is 261874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.024 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000297679.10. 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
	HSD3B7	NM_025193.4	MANE Select	c.804C>T	p.Tyr268Tyr	synonymous	Exon 7 of 7	NP_079469.2
	HSD3B7	NM_001142777.2		c.*50C>T		3_prime_UTR	Exon 6 of 6	NP_001136249.1
	HSD3B7	NM_001142778.2		c.*50C>T		3_prime_UTR	Exon 6 of 6	NP_001136250.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD3B7	ENST00000297679.10	TSL:1 MANE Select	c.804C>T	p.Tyr268Tyr	synonymous	Exon 7 of 7	ENSP00000297679.5
	ENSG00000279196	ENST00000624286.1	TSL:6	n.394G>A		non_coding_transcript_exon	Exon 1 of 1
	HSD3B7	ENST00000262520.10	TSL:2	c.*50C>T		3_prime_UTR	Exon 6 of 6	ENSP00000262520.6

Frequencies

GnomAD3 genomes AF: 0.0682 AC: 10388 AN: 152206 Hom.: 480 Cov.: 34

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0518

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.0691

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0636

GnomAD2 exomes AF: 0.0696 AC: 17471 AN: 251178 AF XY: 0.0707

Gnomad AFR exome AF: 0.0173

Gnomad AMR exome AF: 0.0380

Gnomad ASJ exome AF: 0.0746

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.0696

Gnomad NFE exome AF: 0.106

Gnomad OTH exome AF: 0.0799

GnomAD4 exome AF: 0.0967 AC: 141269 AN: 1461526 Hom.: 7649 Cov.: 65 AF XY: 0.0944 AC XY: 68633 AN XY: 727122

African (AFR) AF: 0.0162 AC: 542 AN: 33478

American (AMR) AF: 0.0404 AC: 1809 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0728 AC: 1901 AN: 26128

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39698

South Asian (SAS) AF: 0.0369 AC: 3185 AN: 86258

European-Finnish (FIN) AF: 0.0693 AC: 3684 AN: 53130

Middle Eastern (MID) AF: 0.0739 AC: 426 AN: 5768

European-Non Finnish (NFE) AF: 0.112 AC: 124591 AN: 1111954

Other (OTH) AF: 0.0847 AC: 5117 AN: 60390

GnomAD4 genome AF: 0.0682 AC: 10383 AN: 152324 Hom.: 480 Cov.: 34 AF XY: 0.0654 AC XY: 4872 AN XY: 74490

African (AFR) AF: 0.0186 AC: 773 AN: 41578

American (AMR) AF: 0.0517 AC: 791 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0680 AC: 236 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0360 AC: 174 AN: 4830

European-Finnish (FIN) AF: 0.0691 AC: 734 AN: 10624

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7501 AN: 68016

Other (OTH) AF: 0.0630 AC: 133 AN: 2112

Alfa AF: 0.0879 Hom.: 515

Bravo AF: 0.0652

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.1
DANN	Benign	0.85
PhyloP100		-0.024
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17849880; hg19: chr16-30999198; COSMIC: COSV52681027; COSMIC: COSV52681027;