NM_001047.4:c.294-8069C>T

Variant names:

• chr5-6643773-C-T
• rs4702379
• NM_001047.4:c.294-8069C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001047.4(SRD5A1):​c.294-8069C>T 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 151,994 control chromosomes in the GnomAD database, including 3,240 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 (3240 hom., cov: 32)
• Consequence: SRD5A1 NM_001047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.294-8069C>T		intron_variant	Intron 1 of 4	ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.319+9904C>T		intron_variant	Intron 1 of 3		NP_001311251.1
SRD5A1	NM_001324323.2	c.-428-1035C>T		intron_variant	Intron 1 of 5		NP_001311252.1
SRD5A1	NR_136739.2	n.431-8069C>T		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.294-8069C>T		intron_variant	Intron 1 of 4	1	NM_001047.4	ENSP00000274192.5
SRD5A1	ENST00000504286.2	n.294-8069C>T		intron_variant	Intron 1 of 5	2		ENSP00000518753.1
SRD5A1	ENST00000510531.6	n.294-1035C>T		intron_variant	Intron 1 of 5	2		ENSP00000425330.1
SRD5A1	ENST00000513117.1	n.293+9904C>T		intron_variant	Intron 1 of 3	2		ENSP00000421342.1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28737 AN: 151876 Hom.: 3240 Cov.: 32

Gnomad AFR AF: 0.0840

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.189 AC: 28738 AN: 151994 Hom.: 3240 Cov.: 32 AF XY: 0.194 AC XY: 14400 AN XY: 74294

African (AFR) AF: 0.0839 AC: 3483 AN: 41498

American (AMR) AF: 0.191 AC: 2921 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 813 AN: 3472

East Asian (EAS) AF: 0.484 AC: 2488 AN: 5140

South Asian (SAS) AF: 0.305 AC: 1472 AN: 4822

European-Finnish (FIN) AF: 0.221 AC: 2325 AN: 10530

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14625 AN: 67958

Other (OTH) AF: 0.210 AC: 442 AN: 2100

Alfa AF: 0.202 Hom.: 2846

Bravo AF: 0.181

Asia WGS AF: 0.317 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.53
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4702379; hg19: chr5-6643886;