rs34212827

Variant names:

• chr16-30988113-T-C
• rs34212827
• NM_025193.4:c.1040T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-30988113-T-C
• chr16-30988113-T-G

Variant summary

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

The NM_025193.4(HSD3B7):​c.1040T>C​(p.Leu347Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 1,606,266 control chromosomes in the GnomAD database, including 3,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (1864 hom., cov: 34)
  • Exomes 𝑓: 0.015 (1672 hom.)
• Consequence: HSD3B7 NM_025193.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.94
• Publications: 15 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 (MetaRNN=0.0014500916).
• BP6: Variant 16-30988113-T-C is Benign according to our data. Variant chr16-30988113-T-C is described in ClinVar as Benign. ClinVar VariationId is 261869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025193.4. 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
	HSD3B7	NM_025193.4	MANE Select	c.1040T>C	p.Leu347Pro	missense	Exon 7 of 7	NP_079469.2
	HSD3B7	NM_001142777.2		c.*286T>C		3_prime_UTR	Exon 6 of 6	NP_001136249.1	Q9H2F3-2
	HSD3B7	NM_001142778.2		c.*286T>C		3_prime_UTR	Exon 6 of 6	NP_001136250.1	Q9H2F3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD3B7	ENST00000297679.10	TSL:1 MANE Select	c.1040T>C	p.Leu347Pro	missense	Exon 7 of 7	ENSP00000297679.5	Q9H2F3-1
	HSD3B7	ENST00000867909.1		c.1163T>C	p.Leu388Pro	missense	Exon 7 of 7	ENSP00000537968.1
	HSD3B7	ENST00000867910.1		c.1163T>C	p.Leu388Pro	missense	Exon 7 of 7	ENSP00000537969.1

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 13695 AN: 152194 Hom.: 1858 Cov.: 34

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.0392

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00760

Gnomad OTH AF: 0.0664

GnomAD2 exomes AF: 0.0281 AC: 6886 AN: 245154 AF XY: 0.0218

Gnomad AFR exome AF: 0.308

Gnomad AMR exome AF: 0.0203

Gnomad ASJ exome AF: 0.00728

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.000767

Gnomad NFE exome AF: 0.00741

Gnomad OTH exome AF: 0.0176

GnomAD4 exome AF: 0.0147 AC: 21374 AN: 1453954 Hom.: 1672 Cov.: 64 AF XY: 0.0137 AC XY: 9877 AN XY: 723110

African (AFR) AF: 0.306 AC: 10240 AN: 33410

American (AMR) AF: 0.0224 AC: 1000 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00797 AC: 208 AN: 26114

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39642

South Asian (SAS) AF: 0.00675 AC: 582 AN: 86192

European-Finnish (FIN) AF: 0.000819 AC: 39 AN: 47614

Middle Eastern (MID) AF: 0.0283 AC: 163 AN: 5760

European-Non Finnish (NFE) AF: 0.00688 AC: 7636 AN: 1110320

Other (OTH) AF: 0.0249 AC: 1503 AN: 60260

GnomAD4 genome AF: 0.0901 AC: 13717 AN: 152312 Hom.: 1864 Cov.: 34 AF XY: 0.0867 AC XY: 6455 AN XY: 74488

African (AFR) AF: 0.297 AC: 12353 AN: 41560

American (AMR) AF: 0.0391 AC: 599 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4830

European-Finnish (FIN) AF: 0.000753 AC: 8 AN: 10618

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00760 AC: 517 AN: 68024

Other (OTH) AF: 0.0658 AC: 139 AN: 2114

Alfa AF: 0.0355 Hom.: 1637

Bravo AF: 0.103

TwinsUK AF: 0.00674 AC: 25

ALSPAC AF: 0.00778 AC: 30

ESP6500AA AF: 0.289 AC: 1271

ESP6500EA AF: 0.00953 AC: 82

ExAC AF: 0.0331 AC: 4012

Asia WGS AF: 0.0290 AC: 101 AN: 3478

EpiCase AF: 0.00938

EpiControl AF: 0.0106

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.9
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.24
MPC		1.1
ClinPred		0.034	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.97
Mutation Taster		=85/15	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: rs34212827; hg19: chr16-30999434;