rs472402

Positions:

• chr5-6635478-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.293+1609G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,670 control chromosomes in the GnomAD database, including 20,970 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 (20970 hom., cov: 33)
• Consequence: SRD5A1 NM_001047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333

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 (AMR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.293+1609G>C		intron_variant		ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.319+1609G>C		intron_variant			NP_001311251.1
SRD5A1	NM_001324323.2	c.-429+1609G>C		intron_variant			NP_001311252.1
SRD5A1	NR_136739.2	n.430+1609G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.293+1609G>C		intron_variant		1	NM_001047.4	ENSP00000274192	P1
SRD5A1	ENST00000504286.2	c.293+1609G>C		intron_variant, NMD_transcript_variant		2		ENSP00000518753
SRD5A1	ENST00000510531.6	c.293+1609G>C		intron_variant, NMD_transcript_variant		2		ENSP00000425330
SRD5A1	ENST00000513117.1	c.293+1609G>C		intron_variant, NMD_transcript_variant		2		ENSP00000421342

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79348 AN: 151550 Hom.: 20951 Cov.: 33

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.524 AC: 79415 AN: 151670 Hom.: 20970 Cov.: 33 AF XY: 0.521 AC XY: 38606 AN XY: 74088

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.526

Alfa AF: 0.522 Hom.: 2555

Bravo AF: 0.529

Asia WGS AF: 0.440 AC: 1533 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	1.7
DANN	Benign	0.27

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: rs472402; hg19: chr5-6635591; COSMIC: COSV52954402; COSMIC: COSV52954402;