rs8192186

chr5-6651896-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.348G>A(p.Ala116=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,612,270 control chromosomes in the GnomAD database, including 106,895 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 (9390 hom., cov: 32)
  • Exomes 𝑓: 0.36 (97505 hom.)
• Consequence: SRD5A1 NM_001047.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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=-0.86).
• BP7: Synonymous conserved (PhyloP=-1.75 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.348G>A	p.Ala116=	synonymous_variant	2/5	ENST00000274192.7
SRD5A1	NM_001324323.2	c.129G>A	p.Ala43=	synonymous_variant	3/6
SRD5A1	NM_001324322.2	c.320-4182G>A		intron_variant
SRD5A1	NR_136739.2	n.485G>A		non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A1	ENST00000274192.7	c.348G>A	p.Ala116=	synonymous_variant	2/5	1	NM_001047.4	P1
SRD5A1	ENST00000504286.2	c.348G>A	p.Ala116=	synonymous_variant, NMD_transcript_variant	2/6	2
SRD5A1	ENST00000510531.6	c.*469G>A		3_prime_UTR_variant, NMD_transcript_variant	3/6	2
SRD5A1	ENST00000513117.1	c.294-4182G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52786 AN: 151970 Hom.: 9377 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.368

GnomAD3 exomes AF: 0.332 AC: 83173 AN: 250850 Hom.: 14577 AF XY: 0.330 AC XY: 44711 AN XY: 135574

Gnomad AFR exome AF: 0.333

Gnomad AMR exome AF: 0.334

Gnomad ASJ exome AF: 0.462

Gnomad EAS exome AF: 0.171

Gnomad SAS exome AF: 0.230

Gnomad FIN exome AF: 0.311

Gnomad NFE exome AF: 0.375

Gnomad OTH exome AF: 0.362

GnomAD4 exome AF: 0.360 AC: 525389 AN: 1460182 Hom.: 97505 Cov.: 38 AF XY: 0.356 AC XY: 258893 AN XY: 726404

Gnomad4 AFR exome AF: 0.342

Gnomad4 AMR exome AF: 0.337

Gnomad4 ASJ exome AF: 0.460

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.315

Gnomad4 NFE exome AF: 0.378

Gnomad4 OTH exome AF: 0.356

GnomAD4 genome AF: 0.347 AC: 52838 AN: 152088 Hom.: 9390 Cov.: 32 AF XY: 0.341 AC XY: 25392 AN XY: 74356

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.369

Alfa AF: 0.372 Hom.: 7395

Bravo AF: 0.354

Asia WGS AF: 0.196 AC: 685 AN: 3478

EpiCase AF: 0.388

EpiControl AF: 0.393

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.39
Dann	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs8192186; hg19: chr5-6652009; COSMIC: COSV57013394;