chr5-6635692-C-G

Position:

• chr5-6635692-C-G

Variant summary

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

The NM_001047.4(SRD5A1):​c.293+1823C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,266 control chromosomes in the GnomAD database, including 3,285 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 0.19 (3285 hom., cov: 35)
• Consequence: SRD5A1 NM_001047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.603

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 (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.293+1823C>G		intron_variant		ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.319+1823C>G		intron_variant			NP_001311251.1
SRD5A1	NM_001324323.2	c.-429+1823C>G		intron_variant			NP_001311252.1
SRD5A1	NR_136739.2	n.430+1823C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.293+1823C>G		intron_variant		1	NM_001047.4	ENSP00000274192	P1
SRD5A1	ENST00000504286.2	c.293+1823C>G		intron_variant, NMD_transcript_variant		2		ENSP00000518753
SRD5A1	ENST00000510531.6	c.293+1823C>G		intron_variant, NMD_transcript_variant		2		ENSP00000425330
SRD5A1	ENST00000513117.1	c.293+1823C>G		intron_variant, NMD_transcript_variant		2		ENSP00000421342

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28851 AN: 152148 Hom.: 3285 Cov.: 35

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.189 AC: 28852 AN: 152266 Hom.: 3285 Cov.: 35 AF XY: 0.194 AC XY: 14469 AN XY: 74446

Gnomad4 AFR AF: 0.0838

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.210

Alfa AF: 0.193 Hom.: 385

Bravo AF: 0.182

Asia WGS AF: 0.319 AC: 1109 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	5.3
DANN	Benign	0.71

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: rs1560149; hg19: chr5-6635805;