chr5-6640484-A-G

Variant names:

• chr5-6640484-A-G
• rs2677933
• NM_001047.4:c.293+6615A>G

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+6615A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 151,678 control chromosomes in the GnomAD database, including 1,723 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 0.14 (1723 hom., cov: 32)
• Consequence: SRD5A1 NM_001047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 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+6615A>G		intron	N/A	NP_001038.1
	SRD5A1	NM_001324322.2		c.319+6615A>G		intron	N/A	NP_001311251.1
	SRD5A1	NM_001324323.2		c.-428-4324A>G		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+6615A>G		intron	N/A	ENSP00000274192.5
	SRD5A1	ENST00000504286.2	TSL:2	n.293+6615A>G		intron	N/A	ENSP00000518753.1
	SRD5A1	ENST00000510531.6	TSL:2	n.294-4324A>G		intron	N/A	ENSP00000425330.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21815 AN: 151580 Hom.: 1720 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.0646

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.144 AC: 21818 AN: 151678 Hom.: 1723 Cov.: 32 AF XY: 0.149 AC XY: 11036 AN XY: 74074

African (AFR) AF: 0.122 AC: 5041 AN: 41326

American (AMR) AF: 0.199 AC: 3027 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.0646 AC: 224 AN: 3468

East Asian (EAS) AF: 0.226 AC: 1166 AN: 5150

South Asian (SAS) AF: 0.164 AC: 787 AN: 4812

European-Finnish (FIN) AF: 0.233 AC: 2435 AN: 10440

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.129 AC: 8746 AN: 67930

Other (OTH) AF: 0.121 AC: 256 AN: 2108

Alfa AF: 0.113 Hom.: 294

Bravo AF: 0.141

Asia WGS AF: 0.236 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.27
DANN	Benign	0.81
PhyloP100		-0.66
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: rs2677933; hg19: chr5-6640597;