rs501999

Positions:

• chr5-6635488-T-C

Variant summary

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

The NM_001047.4(SRD5A1):​c.293+1619T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,692 control chromosomes in the GnomAD database, including 20,948 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 0.52 (20948 hom., cov: 33)
• Consequence: SRD5A1 NM_001047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.75

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A1	NM_001047.4	c.293+1619T>C		intron_variant		ENST00000274192.7
SRD5A1	NM_001324322.2	c.319+1619T>C		intron_variant
SRD5A1	NM_001324323.2	c.-429+1619T>C		intron_variant
SRD5A1	NR_136739.2	n.430+1619T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A1	ENST00000274192.7	c.293+1619T>C		intron_variant		1	NM_001047.4	P1
SRD5A1	ENST00000504286.2	c.293+1619T>C		intron_variant, NMD_transcript_variant		2
SRD5A1	ENST00000510531.6	c.293+1619T>C		intron_variant, NMD_transcript_variant		2
SRD5A1	ENST00000513117.1	c.293+1619T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79309 AN: 151572 Hom.: 20929 Cov.: 33

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.523 AC: 79376 AN: 151692 Hom.: 20948 Cov.: 33 AF XY: 0.521 AC XY: 38589 AN XY: 74114

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.525

Alfa AF: 0.522 Hom.: 2552

Bravo AF: 0.529

Asia WGS AF: 0.440 AC: 1532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.81
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: rs501999; hg19: chr5-6635601; COSMIC: COSV52954407; COSMIC: COSV52954407;