rs8192236

Positions:

• chr5-6665880-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.714-2322G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 152,302 control chromosomes in the GnomAD database, including 101 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 0.030 (101 hom., cov: 33)
• Consequence: SRD5A1 NM_001047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77

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 (AFR) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.714-2322G>C		intron_variant		ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.573-2322G>C		intron_variant			NP_001311251.1
SRD5A1	NM_001324323.2	c.495-2322G>C		intron_variant			NP_001311252.1
SRD5A1	NR_136739.2	n.1041-2322G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.714-2322G>C		intron_variant		1	NM_001047.4	ENSP00000274192	P1
SRD5A1	ENST00000504286.2	c.*139-2322G>C		intron_variant, NMD_transcript_variant		2		ENSP00000518753
SRD5A1	ENST00000510531.6	c.*835-2322G>C		intron_variant, NMD_transcript_variant		2		ENSP00000425330
SRD5A1	ENST00000513117.1	c.*139-2322G>C		intron_variant, NMD_transcript_variant		2		ENSP00000421342

Frequencies

GnomAD3 genomes AF: 0.0302 AC: 4600 AN: 152184 Hom.: 99 Cov.: 33

Gnomad AFR AF: 0.0535

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0257

Gnomad OTH AF: 0.0253

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

GnomAD4 genome AF: 0.0303 AC: 4622 AN: 152302 Hom.: 101 Cov.: 33 AF XY: 0.0289 AC XY: 2151 AN XY: 74472

Gnomad4 AFR AF: 0.0539

Gnomad4 AMR AF: 0.0147

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0247

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.0257

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0271 Hom.: 8

Bravo AF: 0.0311

Asia WGS AF: 0.0150 AC: 53 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	0.049
DANN	Benign	0.22

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: rs8192236; hg19: chr5-6665993;