5-6637830-G-A

Variant names:

• chr5-6637830-G-A
• rs535981
• NM_001047.4:c.293+3961G>A

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+3961G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,080 control chromosomes in the GnomAD database, including 3,019 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 (3019 hom., cov: 33)
• Consequence: SRD5A1 NM_001047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001047.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A1	NM_001047.4	MANE Select	c.293+3961G>A		intron	N/A	NP_001038.1
	SRD5A1	NM_001324322.2		c.319+3961G>A		intron	N/A	NP_001311251.1
	SRD5A1	NM_001324323.2		c.-429+3961G>A		intron	N/A	NP_001311252.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A1	ENST00000274192.7	TSL:1 MANE Select	c.293+3961G>A		intron	N/A	ENSP00000274192.5
	SRD5A1	ENST00000504286.2	TSL:2	n.293+3961G>A		intron	N/A	ENSP00000518753.1
	SRD5A1	ENST00000510531.6	TSL:2	n.293+3961G>A		intron	N/A	ENSP00000425330.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29215 AN: 151964 Hom.: 3015 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.192 AC: 29236 AN: 152080 Hom.: 3019 Cov.: 33 AF XY: 0.195 AC XY: 14525 AN XY: 74324

African (AFR) AF: 0.234 AC: 9699 AN: 41476

American (AMR) AF: 0.222 AC: 3393 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3472

East Asian (EAS) AF: 0.225 AC: 1160 AN: 5150

South Asian (SAS) AF: 0.190 AC: 917 AN: 4820

European-Finnish (FIN) AF: 0.249 AC: 2628 AN: 10568

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

European-Non Finnish (NFE) AF: 0.157 AC: 10646 AN: 67992

Other (OTH) AF: 0.165 AC: 349 AN: 2116

Alfa AF: 0.174 Hom.: 4024

Bravo AF: 0.192

Asia WGS AF: 0.256 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.60
PhyloP100		0.41
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: rs535981; hg19: chr5-6637943;