rs2305880

Variant names:

• chr16-30988141-T-C
• rs2305880
• NM_025193.4:c.1068T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-30988141-T-C
• chr16-30988141-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_025193.4(HSD3B7):​c.1068T>C​(p.Arg356Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 1,605,016 control chromosomes in the GnomAD database, including 302,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (23616 hom., cov: 33)
  • Exomes 𝑓: 0.61 (278464 hom.)
• Consequence: HSD3B7 NM_025193.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.85
• Publications: 41 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet

ENSG00000279196 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 16-30988141-T-C is Benign according to our data. Variant chr16-30988141-T-C is described in ClinVar as Benign. ClinVar VariationId is 261870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.86 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 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.1068T>C	p.Arg356Arg	synonymous	Exon 7 of 7	NP_079469.2
	HSD3B7	NM_001142777.2		c.*314T>C		3_prime_UTR	Exon 6 of 6	NP_001136249.1	Q9H2F3-2
	HSD3B7	NM_001142778.2		c.*314T>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.1068T>C	p.Arg356Arg	synonymous	Exon 7 of 7	ENSP00000297679.5	Q9H2F3-1
	HSD3B7	ENST00000867909.1		c.1191T>C	p.Arg397Arg	synonymous	Exon 7 of 7	ENSP00000537968.1
	HSD3B7	ENST00000867910.1		c.1191T>C	p.Arg397Arg	synonymous	Exon 7 of 7	ENSP00000537969.1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80507 AN: 152070 Hom.: 23600 Cov.: 33

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.593

GnomAD2 exomes AF: 0.587 AC: 141223 AN: 240682 AF XY: 0.581

Gnomad AFR exome AF: 0.263

Gnomad AMR exome AF: 0.564

Gnomad ASJ exome AF: 0.674

Gnomad EAS exome AF: 0.910

Gnomad FIN exome AF: 0.659

Gnomad NFE exome AF: 0.638

Gnomad OTH exome AF: 0.611

GnomAD4 exome AF: 0.610 AC: 886154 AN: 1452828 Hom.: 278464 Cov.: 60 AF XY: 0.604 AC XY: 436546 AN XY: 722678

African (AFR) AF: 0.265 AC: 8842 AN: 33416

American (AMR) AF: 0.567 AC: 25105 AN: 44294

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 17546 AN: 26090

East Asian (EAS) AF: 0.910 AC: 36042 AN: 39606

South Asian (SAS) AF: 0.333 AC: 28583 AN: 85914

European-Finnish (FIN) AF: 0.654 AC: 30773 AN: 47042

Middle Eastern (MID) AF: 0.700 AC: 4034 AN: 5764

European-Non Finnish (NFE) AF: 0.629 AC: 698514 AN: 1110480

Other (OTH) AF: 0.610 AC: 36715 AN: 60222

GnomAD4 genome AF: 0.529 AC: 80568 AN: 152188 Hom.: 23616 Cov.: 33 AF XY: 0.531 AC XY: 39477 AN XY: 74398

African (AFR) AF: 0.279 AC: 11595 AN: 41538

American (AMR) AF: 0.571 AC: 8732 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2397 AN: 3472

East Asian (EAS) AF: 0.906 AC: 4680 AN: 5164

South Asian (SAS) AF: 0.309 AC: 1492 AN: 4824

European-Finnish (FIN) AF: 0.668 AC: 7082 AN: 10596

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42550 AN: 67974

Other (OTH) AF: 0.590 AC: 1247 AN: 2114

Alfa AF: 0.610 Hom.: 42872

Bravo AF: 0.520

Asia WGS AF: 0.547 AC: 1907 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)
-	-	1	Congenital bile acid synthesis defect 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.63
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs2305880; hg19: chr16-30999462; COSMIC: COSV52679757; COSMIC: COSV52679757;