5-6666971-T-C

Variant names:

• chr5-6666971-T-C
• rs3797177
• NM_001047.4:c.714-1231T>C

Variant summary

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

The NM_001047.4(SRD5A1):​c.714-1231T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,240 control chromosomes in the GnomAD database, including 3,418 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 (3418 hom., cov: 33)
• Consequence: SRD5A1 NM_001047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.714-1231T>C		intron_variant	Intron 4 of 4	ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.573-1231T>C		intron_variant	Intron 3 of 3		NP_001311251.1
SRD5A1	NM_001324323.2	c.495-1231T>C		intron_variant	Intron 5 of 5		NP_001311252.1
SRD5A1	NR_136739.2	n.1041-1231T>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.714-1231T>C		intron_variant	Intron 4 of 4	1	NM_001047.4	ENSP00000274192.5
SRD5A1	ENST00000504286.2	n.*139-1231T>C		intron_variant	Intron 5 of 5	2		ENSP00000518753.1
SRD5A1	ENST00000510531.6	n.*835-1231T>C		intron_variant	Intron 5 of 5	2		ENSP00000425330.1
SRD5A1	ENST00000513117.1	n.*139-1231T>C		intron_variant	Intron 3 of 3	2		ENSP00000421342.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29564 AN: 152122 Hom.: 3417 Cov.: 33

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.0907

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.194 AC: 29593 AN: 152240 Hom.: 3418 Cov.: 33 AF XY: 0.193 AC XY: 14379 AN XY: 74448

African (AFR) AF: 0.328 AC: 13606 AN: 41516

American (AMR) AF: 0.128 AC: 1951 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 496 AN: 3470

East Asian (EAS) AF: 0.226 AC: 1172 AN: 5176

South Asian (SAS) AF: 0.0910 AC: 439 AN: 4824

European-Finnish (FIN) AF: 0.148 AC: 1572 AN: 10620

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9812 AN: 68010

Other (OTH) AF: 0.185 AC: 392 AN: 2116

Alfa AF: 0.110 Hom.: 273

Bravo AF: 0.198

Asia WGS AF: 0.135 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.32
DANN	Benign	0.16
PhyloP100		-1.3
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: rs3797177; hg19: chr5-6667084;