chr16-30985474-C-T

Variant names:

• chr16-30985474-C-T
• rs79974799
• NM_025193.4:c.-7+177C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001142777.2(HSD3B7):​c.-185C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0955 in 1,486,078 control chromosomes in the GnomAD database, including 7,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (479 hom., cov: 33)
  • Exomes 𝑓: 0.099 (7188 hom.)
• Consequence: HSD3B7 NM_001142777.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.15
• Publications: 8 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, Labcorp Genetics (formerly Invitae), G2P

ENSG00000279196 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-30985474-C-T is Benign according to our data. Variant chr16-30985474-C-T is described in ClinVar as Benign. ClinVar VariationId is 1281644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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: NM_001142777.2. 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
	HSD3B7	NM_025193.4	MANE Select	c.-7+177C>T		intron	N/A	NP_079469.2
	HSD3B7	NM_001142777.2		c.-185C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001136249.1	Q9H2F3-2
	HSD3B7	NM_001142777.2		c.-185C>T		5_prime_UTR	Exon 2 of 6	NP_001136249.1	Q9H2F3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD3B7	ENST00000297679.10	TSL:1 MANE Select	c.-7+177C>T		intron	N/A	ENSP00000297679.5	Q9H2F3-1
	HSD3B7	ENST00000949919.1		c.-185C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000619978.1
	HSD3B7	ENST00000867903.1		c.-185C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	ENSP00000537962.1

Frequencies

GnomAD3 genomes AF: 0.0684 AC: 10417 AN: 152184 Hom.: 479 Cov.: 33

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0519

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0636

GnomAD2 exomes AF: 0.0636 AC: 6559 AN: 103194 AF XY: 0.0651

Gnomad AFR exome AF: 0.0168

Gnomad AMR exome AF: 0.0374

Gnomad ASJ exome AF: 0.0768

Gnomad EAS exome AF: 0.000391

Gnomad FIN exome AF: 0.0638

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.0731

GnomAD4 exome AF: 0.0986 AC: 131478 AN: 1333776 Hom.: 7188 Cov.: 31 AF XY: 0.0964 AC XY: 62865 AN XY: 652024

African (AFR) AF: 0.0164 AC: 502 AN: 30588

American (AMR) AF: 0.0401 AC: 1289 AN: 32148

Ashkenazi Jewish (ASJ) AF: 0.0719 AC: 1567 AN: 21800

East Asian (EAS) AF: 0.000313 AC: 11 AN: 35136

South Asian (SAS) AF: 0.0371 AC: 2610 AN: 70416

European-Finnish (FIN) AF: 0.0688 AC: 2182 AN: 31714

Middle Eastern (MID) AF: 0.0744 AC: 285 AN: 3832

European-Non Finnish (NFE) AF: 0.112 AC: 118308 AN: 1052602

Other (OTH) AF: 0.0851 AC: 4724 AN: 55540

GnomAD4 genome AF: 0.0684 AC: 10412 AN: 152302 Hom.: 479 Cov.: 33 AF XY: 0.0655 AC XY: 4879 AN XY: 74476

African (AFR) AF: 0.0192 AC: 798 AN: 41572

American (AMR) AF: 0.0518 AC: 793 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0677 AC: 235 AN: 3472

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

South Asian (SAS) AF: 0.0361 AC: 174 AN: 4826

European-Finnish (FIN) AF: 0.0689 AC: 732 AN: 10618

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

European-Non Finnish (NFE) AF: 0.110 AC: 7506 AN: 68004

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

Alfa AF: 0.0804 Hom.: 261

Bravo AF: 0.0654

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.68
PhyloP100		-1.1
PromoterAI		-0.036	Neutral
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)		0.050		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: rs79974799; hg19: chr16-30996795;