chr5-6639066-A-T

Variant names:

• chr5-6639066-A-T
• rs494958
• NM_001047.4:c.293+5197A>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.293+5197A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,188 control chromosomes in the GnomAD database, including 3,573 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 0.21 (3573 hom., cov: 33)
• Consequence: SRD5A1 NM_001047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.83
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.293+5197A>T		intron_variant	Intron 1 of 4	ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.319+5197A>T		intron_variant	Intron 1 of 3		NP_001311251.1
SRD5A1	NM_001324323.2	c.-429+5197A>T		intron_variant	Intron 1 of 5		NP_001311252.1
SRD5A1	NR_136739.2	n.430+5197A>T		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.293+5197A>T		intron_variant	Intron 1 of 4	1	NM_001047.4	ENSP00000274192.5
SRD5A1	ENST00000504286.2	n.293+5197A>T		intron_variant	Intron 1 of 5	2		ENSP00000518753.1
SRD5A1	ENST00000510531.6	n.293+5197A>T		intron_variant	Intron 1 of 5	2		ENSP00000425330.1
SRD5A1	ENST00000513117.1	n.293+5197A>T		intron_variant	Intron 1 of 3	2		ENSP00000421342.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31338 AN: 152070 Hom.: 3567 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.206 AC: 31369 AN: 152188 Hom.: 3573 Cov.: 33 AF XY: 0.209 AC XY: 15519 AN XY: 74388

African (AFR) AF: 0.281 AC: 11663 AN: 41512

American (AMR) AF: 0.229 AC: 3496 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3470

East Asian (EAS) AF: 0.228 AC: 1183 AN: 5182

South Asian (SAS) AF: 0.191 AC: 920 AN: 4818

European-Finnish (FIN) AF: 0.249 AC: 2637 AN: 10582

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10659 AN: 68008

Other (OTH) AF: 0.173 AC: 367 AN: 2116

Alfa AF: 0.107 Hom.: 157

Bravo AF: 0.207

Asia WGS AF: 0.261 AC: 905 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.47
PhyloP100		-2.8
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: rs494958; hg19: chr5-6639179;