rs8192139

chr5-6636860-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001047.4(SRD5A1):c.293+2991C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,862 control chromosomes in the GnomAD database, including 12,190 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 0.40 (12190 hom., cov: 31)
• Consequence: SRD5A1 NM_001047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A1	NM_001047.4	c.293+2991C>G		intron_variant		ENST00000274192.7
SRD5A1	NM_001324322.2	c.319+2991C>G		intron_variant
SRD5A1	NM_001324323.2	c.-429+2991C>G		intron_variant
SRD5A1	NR_136739.2	n.430+2991C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A1	ENST00000274192.7	c.293+2991C>G		intron_variant		1	NM_001047.4	P1
SRD5A1	ENST00000504286.2	c.293+2991C>G		intron_variant, NMD_transcript_variant		2
SRD5A1	ENST00000510531.6	c.293+2991C>G		intron_variant, NMD_transcript_variant		2
SRD5A1	ENST00000513117.1	c.293+2991C>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60140 AN: 151744 Hom.: 12177 Cov.: 31

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.418

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.396 AC: 60200 AN: 151862 Hom.: 12190 Cov.: 31 AF XY: 0.390 AC XY: 28921 AN XY: 74238

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.419

Alfa AF: 0.390 Hom.: 1492

Bravo AF: 0.404

Asia WGS AF: 0.266 AC: 928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.0
Dann	Benign	0.40

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: rs8192139; hg19: chr5-6636973;