rs824811

chr5-6665668-G-Achr5-6665668-G-Cchr5-6665668-G-T

Variant summary

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

The NM_001047.4(SRD5A1):c.714-2534G>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 152,088 control chromosomes in the GnomAD database, including 52,887 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 (52887 hom., cov: 32)
• Consequence: SRD5A1 NM_001047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A1	NM_001047.4	c.714-2534G>A		intron_variant		ENST00000274192.7
SRD5A1	NM_001324322.2	c.573-2534G>A		intron_variant
SRD5A1	NM_001324323.2	c.495-2534G>A		intron_variant
SRD5A1	NR_136739.2	n.1041-2534G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A1	ENST00000274192.7	c.714-2534G>A		intron_variant		1	NM_001047.4	P1
SRD5A1	ENST00000504286.2	c.*139-2534G>A		intron_variant, NMD_transcript_variant		2
SRD5A1	ENST00000510531.6	c.*835-2534G>A		intron_variant, NMD_transcript_variant		2
SRD5A1	ENST00000513117.1	c.*139-2534G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.829 AC: 126027 AN: 151970 Hom.: 52845 Cov.: 32

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.816

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

GnomAD4 genome AF: 0.829 AC: 126129 AN: 152088 Hom.: 52887 Cov.: 32 AF XY: 0.828 AC XY: 61514 AN XY: 74298

Gnomad4 AFR AF: 0.951

Gnomad4 AMR AF: 0.817

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.816

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.818

Alfa AF: 0.656 Hom.: 1337

Bravo AF: 0.840

Asia WGS AF: 0.840 AC: 2923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.18
Dann	Benign	0.46

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: rs824811; hg19: chr5-6665781;