5-6651839-A-C

Variant names:

• chr5-6651839-A-C
• rs186093099
• NM_001047.4:c.294-3A>C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001047.4(SRD5A1):​c.294-3A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00529 in 1,603,690 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0048 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0053 (42 hom.)
• Consequence: SRD5A1 NM_001047.4 splice_region, intron
• Scores: Splicing: ADA: 0.00003695
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.294-3A>C		splice_region_variant, intron_variant	Intron 1 of 4	ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.320-4239A>C		intron_variant	Intron 1 of 3		NP_001311251.1
SRD5A1	NM_001324323.2	c.75-3A>C		splice_region_variant, intron_variant	Intron 2 of 5		NP_001311252.1
SRD5A1	NR_136739.2	n.431-3A>C		splice_region_variant, intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.294-3A>C		splice_region_variant, intron_variant	Intron 1 of 4	1	NM_001047.4	ENSP00000274192.5
SRD5A1	ENST00000504286.1	n.415-3A>C		splice_region_variant, intron_variant	Intron 1 of 2	2		ENSP00000518753.1
SRD5A1	ENST00000510531.5	n.*415-3A>C		splice_region_variant, intron_variant	Intron 2 of 5	2		ENSP00000425330.1
SRD5A1	ENST00000513117.1	n.294-4239A>C		intron_variant	Intron 1 of 3	2		ENSP00000421342.1

Frequencies

GnomAD3 genomes AF: 0.00484 AC: 736 AN: 152174 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0319

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00495

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00549 AC: 1365 AN: 248536 Hom.: 12 AF XY: 0.00550 AC XY: 739 AN XY: 134256

Gnomad AFR exome AF: 0.000616

Gnomad AMR exome AF: 0.000944

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00147

Gnomad FIN exome AF: 0.0313

Gnomad NFE exome AF: 0.00511

Gnomad OTH exome AF: 0.00431

GnomAD4 exome AF: 0.00534 AC: 7752 AN: 1451398 Hom.: 42 Cov.: 29 AF XY: 0.00524 AC XY: 3772 AN XY: 720466

Gnomad4 AFR exome AF: 0.000722

Gnomad4 AMR exome AF: 0.000929

Gnomad4 ASJ exome AF: 0.000116

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00140

Gnomad4 FIN exome AF: 0.0315

Gnomad4 NFE exome AF: 0.00506

Gnomad4 OTH exome AF: 0.00471

GnomAD4 genome AF: 0.00483 AC: 736 AN: 152292 Hom.: 2 Cov.: 31 AF XY: 0.00595 AC XY: 443 AN XY: 74466

Gnomad4 AFR AF: 0.000866

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0319

Gnomad4 NFE AF: 0.00495

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00443 Hom.: 3

Bravo AF: 0.00252

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000037
dbscSNV1_RF	Benign	0.010
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: rs186093099; hg19: chr5-6651952;