chr5-6656097-G-A

Variant names:

• chr5-6656097-G-A
• rs3736316
• NM_001047.4:c.480G>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.480G>A​(p.Thr160Thr) 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
• Publications: 26 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=-0.77).
• 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A1	NM_001047.4	MANE Select	c.480G>A	p.Thr160Thr	synonymous	Exon 3 of 5	NP_001038.1
	SRD5A1	NM_001324322.2		c.339G>A	p.Thr113Thr	synonymous	Exon 2 of 4	NP_001311251.1
	SRD5A1	NM_001324323.2		c.261G>A	p.Thr87Thr	synonymous	Exon 4 of 6	NP_001311252.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A1	ENST00000274192.7	TSL:1 MANE Select	c.480G>A	p.Thr160Thr	synonymous	Exon 3 of 5	ENSP00000274192.5
	SRD5A1	ENST00000504286.2	TSL:2	n.670G>A		non_coding_transcript_exon	Exon 4 of 6	ENSP00000518753.1
	SRD5A1	ENST00000510531.6	TSL:2	n.*601G>A		non_coding_transcript_exon	Exon 4 of 6	ENSP00000425330.1

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

GnomAD2 exomes AF: 0.330 AC: 82832 AN: 250758 AF XY: 0.328

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 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

African (AFR) AF: 0.344 AC: 11488 AN: 33422

American (AMR) AF: 0.337 AC: 15014 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 12006 AN: 26100

East Asian (EAS) AF: 0.164 AC: 6499 AN: 39668

South Asian (SAS) AF: 0.222 AC: 19146 AN: 86168

European-Finnish (FIN) AF: 0.315 AC: 16831 AN: 53358

Middle Eastern (MID) AF: 0.373 AC: 2148 AN: 5756

European-Non Finnish (NFE) AF: 0.378 AC: 419919 AN: 1110420

Other (OTH) AF: 0.355 AC: 21414 AN: 60326

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

African (AFR) AF: 0.338 AC: 13983 AN: 41398

American (AMR) AF: 0.356 AC: 5421 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1575 AN: 3466

East Asian (EAS) AF: 0.161 AC: 831 AN: 5164

South Asian (SAS) AF: 0.217 AC: 1045 AN: 4822

European-Finnish (FIN) AF: 0.308 AC: 3239 AN: 10514

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

European-Non Finnish (NFE) AF: 0.374 AC: 25414 AN: 67954

Other (OTH) AF: 0.371 AC: 783 AN: 2108

Alfa AF: 0.374 Hom.: 5579

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.19
DANN	Benign	0.91
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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