rs248805

Positions:

• chr5-6644903-A-G

Variant summary

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

The NM_001047.4(SRD5A1):​c.294-6939A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 455,610 control chromosomes in the GnomAD database, including 66,785 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 0.57 (24760 hom., cov: 31)
  • Exomes 𝑓: 0.52 (42025 hom.)
• Consequence: SRD5A1 NM_001047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.426

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A1	NM_001047.4	c.294-6939A>G		intron_variant		ENST00000274192.7
SRD5A1	NM_001324323.2	c.-333A>G		5_prime_UTR_variant	2/6
SRD5A1	NM_001324322.2	c.319+11034A>G		intron_variant
SRD5A1	NR_136739.2	n.431-6939A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A1	ENST00000274192.7	c.294-6939A>G		intron_variant		1	NM_001047.4	P1
SRD5A1	ENST00000504286.2	c.294-6939A>G		intron_variant, NMD_transcript_variant		2
SRD5A1	ENST00000510531.6	c.*8A>G		3_prime_UTR_variant, NMD_transcript_variant	2/6	2
SRD5A1	ENST00000513117.1	c.293+11034A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85737 AN: 151664 Hom.: 24747 Cov.: 31

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.553

GnomAD3 exomes AF: 0.531 AC: 68115 AN: 128288 Hom.: 18512 AF XY: 0.525 AC XY: 36889 AN XY: 70252

Gnomad AFR exome AF: 0.678

Gnomad AMR exome AF: 0.615

Gnomad ASJ exome AF: 0.532

Gnomad EAS exome AF: 0.402

Gnomad SAS exome AF: 0.490

Gnomad FIN exome AF: 0.536

Gnomad NFE exome AF: 0.516

Gnomad OTH exome AF: 0.532

GnomAD4 exome AF: 0.521 AC: 158419 AN: 303828 Hom.: 42025 Cov.: 0 AF XY: 0.516 AC XY: 89248 AN XY: 172994

Gnomad4 AFR exome AF: 0.673

Gnomad4 AMR exome AF: 0.616

Gnomad4 ASJ exome AF: 0.532

Gnomad4 EAS exome AF: 0.406

Gnomad4 SAS exome AF: 0.486

Gnomad4 FIN exome AF: 0.541

Gnomad4 NFE exome AF: 0.515

Gnomad4 OTH exome AF: 0.521

GnomAD4 genome AF: 0.565 AC: 85805 AN: 151782 Hom.: 24760 Cov.: 31 AF XY: 0.563 AC XY: 41731 AN XY: 74136

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.553

Alfa AF: 0.529 Hom.: 11077

Bravo AF: 0.575

Asia WGS AF: 0.505 AC: 1757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.63

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: rs248805; hg19: chr5-6645016; COSMIC: COSV57014068;