chr5-6643734-G-A

Variant names:

• chr5-6643734-G-A
• rs166050
• NM_001047.4:c.294-8108G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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 -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.

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.294-8108G>A		intron	N/A	NP_001038.1
	SRD5A1	NM_001324322.2		c.319+9865G>A		intron	N/A	NP_001311251.1
	SRD5A1	NM_001324323.2		c.-428-1074G>A		intron	N/A	NP_001311252.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A1	ENST00000274192.7	TSL:1 MANE Select	c.294-8108G>A		intron	N/A	ENSP00000274192.5
	SRD5A1	ENST00000504286.2	TSL:2	n.294-8108G>A		intron	N/A	ENSP00000518753.1
	SRD5A1	ENST00000510531.6	TSL:2	n.294-1074G>A		intron	N/A	ENSP00000425330.1

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

African (AFR) AF: 0.955 AC: 39694 AN: 41548

American (AMR) AF: 0.818 AC: 12503 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2702 AN: 3472

East Asian (EAS) AF: 0.898 AC: 4641 AN: 5166

South Asian (SAS) AF: 0.814 AC: 3925 AN: 4822

European-Finnish (FIN) AF: 0.783 AC: 8291 AN: 10594

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.761 AC: 51720 AN: 67998

Other (OTH) AF: 0.815 AC: 1717 AN: 2106

Alfa AF: 0.776 Hom.: 91313

Bravo AF: 0.839

Asia WGS AF: 0.844 AC: 2935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.039
DANN	Benign	0.53
PhyloP100		-1.1
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: rs166050; hg19: chr5-6643847;