rs8192186

Variant names:

• chr5-6651896-G-A
• rs8192186
• NM_001047.4:c.348G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001047.4(SRD5A1):​c.348G>A​(p.Ala116Ala) 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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001047.4. 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
	SRD5A1	NM_001047.4	MANE Select	c.348G>A	p.Ala116Ala	synonymous	Exon 2 of 5	NP_001038.1	P18405
	SRD5A1	NM_001324323.2		c.129G>A	p.Ala43Ala	synonymous	Exon 3 of 6	NP_001311252.1
	SRD5A1	NM_001324322.2		c.320-4182G>A		intron	N/A	NP_001311251.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A1	ENST00000274192.7	TSL:1 MANE Select	c.348G>A	p.Ala116Ala	synonymous	Exon 2 of 5	ENSP00000274192.5	P18405
	SRD5A1	ENST00000854432.1		c.348G>A	p.Ala116Ala	synonymous	Exon 2 of 6	ENSP00000524491.1
	SRD5A1	ENST00000854431.1		c.348G>A	p.Ala116Ala	synonymous	Exon 2 of 5	ENSP00000524490.1

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

GnomAD2 exomes AF: 0.332 AC: 83173 AN: 250850 AF XY: 0.330

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 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

African (AFR) AF: 0.342 AC: 11445 AN: 33418

American (AMR) AF: 0.337 AC: 15050 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 12013 AN: 26108

East Asian (EAS) AF: 0.164 AC: 6499 AN: 39682

South Asian (SAS) AF: 0.231 AC: 19885 AN: 86082

European-Finnish (FIN) AF: 0.315 AC: 16838 AN: 53400

Middle Eastern (MID) AF: 0.375 AC: 2101 AN: 5608

European-Non Finnish (NFE) AF: 0.378 AC: 420113 AN: 1110946

Other (OTH) AF: 0.356 AC: 21445 AN: 60310

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

African (AFR) AF: 0.336 AC: 13940 AN: 41456

American (AMR) AF: 0.355 AC: 5426 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1576 AN: 3470

East Asian (EAS) AF: 0.160 AC: 827 AN: 5176

South Asian (SAS) AF: 0.226 AC: 1087 AN: 4820

European-Finnish (FIN) AF: 0.306 AC: 3241 AN: 10582

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25408 AN: 67992

Other (OTH) AF: 0.369 AC: 780 AN: 2114

Alfa AF: 0.371 Hom.: 8248

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.39
DANN	Benign	0.70
PhyloP100		-1.8
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: rs8192186; hg19: chr5-6652009; COSMIC: COSV57013394;