rs3736316

chr5-6656097-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001047.4(SRD5A1):c.480G>A(p.Thr160=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,611,670 control chromosomes in the GnomAD database, including 106,769 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (9402 hom., cov: 32)
  • Exomes 𝑓: 0.36 (97367 hom.)
• Consequence: SRD5A1 NM_001047.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

Genes affected

SRD5A1 (HGNC:11284): (steroid 5 alpha-reductase 1) Steroid 5-alpha-reductase (EC 1.3.99.5) catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT). Also see SRD5A2 (MIM 607306).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-2.27 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A1	NM_001047.4	c.480G>A	p.Thr160=	synonymous_variant	3/5	ENST00000274192.7
SRD5A1	NM_001324322.2	c.339G>A	p.Thr113=	synonymous_variant	2/4
SRD5A1	NM_001324323.2	c.261G>A	p.Thr87=	synonymous_variant	4/6
SRD5A1	NR_136739.2	n.807G>A		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A1	ENST00000274192.7	c.480G>A	p.Thr160=	synonymous_variant	3/5	1	NM_001047.4	P1
SRD5A1	ENST00000504286.2	c.670G>A	p.Gly224Arg	missense_variant, NMD_transcript_variant	4/6	2
SRD5A1	ENST00000513117.1	c.313G>A	p.Gly105Arg	missense_variant, NMD_transcript_variant	2/4	2
SRD5A1	ENST00000510531.6	c.*601G>A		3_prime_UTR_variant, NMD_transcript_variant	4/6	2

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52794 AN: 151758 Hom.: 9390 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.371

GnomAD3 exomes AF: 0.330 AC: 82832 AN: 250758 Hom.: 14468 AF XY: 0.328 AC XY: 44474 AN XY: 135554

Gnomad AFR exome AF: 0.335

Gnomad AMR exome AF: 0.334

Gnomad ASJ exome AF: 0.462

Gnomad EAS exome AF: 0.172

Gnomad SAS exome AF: 0.219

Gnomad FIN exome AF: 0.311

Gnomad NFE exome AF: 0.375

Gnomad OTH exome AF: 0.360

GnomAD4 exome AF: 0.359 AC: 524465 AN: 1459794 Hom.: 97367 Cov.: 33 AF XY: 0.356 AC XY: 258299 AN XY: 726234

Gnomad4 AFR exome AF: 0.344

Gnomad4 AMR exome AF: 0.337

Gnomad4 ASJ exome AF: 0.460

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.315

Gnomad4 NFE exome AF: 0.378

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.348 AC: 52846 AN: 151876 Hom.: 9402 Cov.: 32 AF XY: 0.342 AC XY: 25363 AN XY: 74222

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.371

Alfa AF: 0.374 Hom.: 5545

Bravo AF: 0.355

Asia WGS AF: 0.189 AC: 659 AN: 3478

EpiCase AF: 0.389

EpiControl AF: 0.393

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.19
Dann	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3736316; hg19: chr5-6656210; COSMIC: COSV57013042; COSMIC: COSV57013042;