5-6642243-C-T

Position:

• chr5-6642243-C-T

Variant summary

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

The NM_001047.4(SRD5A1):​c.293+8374C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,830 control chromosomes in the GnomAD database, including 11,302 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 0.38 (11302 hom., cov: 32)
• Consequence: SRD5A1 NM_001047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A1	NM_001047.4	c.293+8374C>T		intron_variant		ENST00000274192.7
SRD5A1	NM_001324322.2	c.319+8374C>T		intron_variant
SRD5A1	NM_001324323.2	c.-428-2565C>T		intron_variant
SRD5A1	NR_136739.2	n.430+8374C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A1	ENST00000274192.7	c.293+8374C>T		intron_variant		1	NM_001047.4	P1
SRD5A1	ENST00000504286.2	c.293+8374C>T		intron_variant, NMD_transcript_variant		2
SRD5A1	ENST00000510531.6	c.294-2565C>T		intron_variant, NMD_transcript_variant		2
SRD5A1	ENST00000513117.1	c.293+8374C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57949 AN: 151712 Hom.: 11289 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.382 AC: 58001 AN: 151830 Hom.: 11302 Cov.: 32 AF XY: 0.376 AC XY: 27869 AN XY: 74194

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.402

Alfa AF: 0.387 Hom.: 4489

Bravo AF: 0.390

Asia WGS AF: 0.254 AC: 886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.65
DANN	Benign	0.60

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: rs8192166; hg19: chr5-6642356;