chr5-6635488-T-C

Variant names:

• chr5-6635488-T-C
• rs501999
• NM_001047.4:c.293+1619T>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.293+1619T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,692 control chromosomes in the GnomAD database, including 20,948 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 0.52 (20948 hom., cov: 33)
• Consequence: SRD5A1 NM_001047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.75
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.293+1619T>C		intron_variant	Intron 1 of 4	ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.319+1619T>C		intron_variant	Intron 1 of 3		NP_001311251.1
SRD5A1	NM_001324323.2	c.-429+1619T>C		intron_variant	Intron 1 of 5		NP_001311252.1
SRD5A1	NR_136739.2	n.430+1619T>C		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.293+1619T>C		intron_variant	Intron 1 of 4	1	NM_001047.4	ENSP00000274192.5
SRD5A1	ENST00000504286.2	n.293+1619T>C		intron_variant	Intron 1 of 5	2		ENSP00000518753.1
SRD5A1	ENST00000510531.6	n.293+1619T>C		intron_variant	Intron 1 of 5	2		ENSP00000425330.1
SRD5A1	ENST00000513117.1	n.293+1619T>C		intron_variant	Intron 1 of 3	2		ENSP00000421342.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79309 AN: 151572 Hom.: 20929 Cov.: 33

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.523 AC: 79376 AN: 151692 Hom.: 20948 Cov.: 33 AF XY: 0.521 AC XY: 38589 AN XY: 74114

African (AFR) AF: 0.515 AC: 21302 AN: 41346

American (AMR) AF: 0.570 AC: 8699 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1852 AN: 3468

East Asian (EAS) AF: 0.384 AC: 1975 AN: 5142

South Asian (SAS) AF: 0.409 AC: 1968 AN: 4816

European-Finnish (FIN) AF: 0.552 AC: 5795 AN: 10496

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 35968 AN: 67860

Other (OTH) AF: 0.525 AC: 1107 AN: 2108

Alfa AF: 0.519 Hom.: 2635

Bravo AF: 0.529

Asia WGS AF: 0.440 AC: 1532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.81
DANN	Benign	0.53
PhyloP100		-3.7
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: rs501999; hg19: chr5-6635601; COSMIC: COSV52954407; COSMIC: COSV52954407;