5-6669649-T-C

Variant names:

• chr5-6669649-T-C
• rs39848
• NM_001047.4:c.*1381T>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.*1381T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,114 control chromosomes in the GnomAD database, including 16,318 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 0.46 (16318 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: SRD5A1 NM_001047.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441
• Publications: 11 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 = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.*1381T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000274192.7	NP_001038.1
SRD5A1	NR_136739.2	n.2488T>C		non_coding_transcript_exon_variant	Exon 6 of 6
SRD5A1	NM_001324322.2	c.*1381T>C		3_prime_UTR_variant	Exon 4 of 4		NP_001311251.1
SRD5A1	NM_001324323.2	c.*1381T>C		3_prime_UTR_variant	Exon 6 of 6		NP_001311252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.*1381T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_001047.4	ENSP00000274192.5
SRD5A1	ENST00000504286.2	n.*1586T>C		non_coding_transcript_exon_variant	Exon 6 of 6	2		ENSP00000518753.1
SRD5A1	ENST00000504286.2	n.*1586T>C		3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000518753.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69572 AN: 151996 Hom.: 16308 Cov.: 33

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.438

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.458 AC: 69626 AN: 152114 Hom.: 16318 Cov.: 33 AF XY: 0.455 AC XY: 33809 AN XY: 74356

African (AFR) AF: 0.530 AC: 22006 AN: 41484

American (AMR) AF: 0.506 AC: 7727 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1439 AN: 3464

East Asian (EAS) AF: 0.275 AC: 1424 AN: 5174

South Asian (SAS) AF: 0.394 AC: 1901 AN: 4822

European-Finnish (FIN) AF: 0.450 AC: 4754 AN: 10576

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28738 AN: 67992

Other (OTH) AF: 0.435 AC: 920 AN: 2114

Alfa AF: 0.435 Hom.: 31832

Bravo AF: 0.469

Asia WGS AF: 0.401 AC: 1396 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	2.3
DANN	Benign	0.49
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism

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: rs39848; hg19: chr5-6669762;