rs16877779

Positions:

• chr5-6670536-G-A
• chr5-6670536-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.*2268G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 152,276 control chromosomes in the GnomAD database, including 499 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 0.076 (499 hom., cov: 33)
  • Exomes 𝑓: 0.031 (0 hom.)
• Consequence: SRD5A1 NM_001047.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.817

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.*2268G>A		3_prime_UTR_variant	5/5	ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.*2268G>A		3_prime_UTR_variant	4/4		NP_001311251.1
SRD5A1	NM_001324323.2	c.*2268G>A		3_prime_UTR_variant	6/6		NP_001311252.1
SRD5A1	NR_136739.2	n.3375G>A		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.*2268G>A		3_prime_UTR_variant	5/5	1	NM_001047.4	ENSP00000274192	P1
SRD5A1	ENST00000504286.2	c.*2473G>A		3_prime_UTR_variant, NMD_transcript_variant	6/6	2		ENSP00000518753

Frequencies

GnomAD3 genomes AF: 0.0756 AC: 11503 AN: 152126 Hom.: 502 Cov.: 33

Gnomad AFR AF: 0.0342

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0679

Gnomad ASJ AF: 0.0959

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.0595

Gnomad FIN AF: 0.0845

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0923

Gnomad OTH AF: 0.0807

GnomAD4 exome AF: 0.0313 AC: 1 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.0357 AC XY: 1 AN XY: 28

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0755 AC: 11499 AN: 152244 Hom.: 499 Cov.: 33 AF XY: 0.0756 AC XY: 5624 AN XY: 74428

Gnomad4 AFR AF: 0.0341

Gnomad4 AMR AF: 0.0677

Gnomad4 ASJ AF: 0.0959

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.0595

Gnomad4 FIN AF: 0.0845

Gnomad4 NFE AF: 0.0923

Gnomad4 OTH AF: 0.0841

Alfa AF: 0.0901 Hom.: 557

Bravo AF: 0.0728

Asia WGS AF: 0.0970 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.97
DANN	Benign	0.37

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: rs16877779; hg19: chr5-6670649;