rs166050

Positions:

• chr5-6643734-G-A
• chr5-6643734-G-C

Variant summary

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

The NM_001047.4(SRD5A1):​c.294-8108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 152,204 control chromosomes in the GnomAD database, including 52,910 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 0.83 (52910 hom., cov: 33)
• Consequence: SRD5A1 NM_001047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.294-8108G>A		intron_variant		ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.319+9865G>A		intron_variant			NP_001311251.1
SRD5A1	NM_001324323.2	c.-428-1074G>A		intron_variant			NP_001311252.1
SRD5A1	NR_136739.2	n.431-8108G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.294-8108G>A		intron_variant		1	NM_001047.4	ENSP00000274192	P1
SRD5A1	ENST00000504286.2	c.294-8108G>A		intron_variant, NMD_transcript_variant		2		ENSP00000518753
SRD5A1	ENST00000510531.6	c.294-1074G>A		intron_variant, NMD_transcript_variant		2		ENSP00000425330
SRD5A1	ENST00000513117.1	c.293+9865G>A		intron_variant, NMD_transcript_variant		2		ENSP00000421342

Frequencies

GnomAD3 genomes AF: 0.829 AC: 126048 AN: 152084 Hom.: 52862 Cov.: 33

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.787

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.813

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

GnomAD4 genome AF: 0.829 AC: 126156 AN: 152204 Hom.: 52910 Cov.: 33 AF XY: 0.828 AC XY: 61646 AN XY: 74410

Gnomad4 AFR AF: 0.955

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.814

Gnomad4 FIN AF: 0.783

Gnomad4 NFE AF: 0.761

Gnomad4 OTH AF: 0.815

Alfa AF: 0.771 Hom.: 65071

Bravo AF: 0.839

Asia WGS AF: 0.844 AC: 2935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.039
DANN	Benign	0.53

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: rs166050; hg19: chr5-6643847;