chr5-6644903-A-G

Variant names:

• chr5-6644903-A-G
• rs248805
• NM_001047.4:c.294-6939A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001047.4(SRD5A1):​c.294-6939A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 455,610 control chromosomes in the GnomAD database, including 66,785 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 0.57 (24760 hom., cov: 31)
  • Exomes 𝑓: 0.52 (42025 hom.)
• Consequence: SRD5A1 NM_001047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.426
• Publications: 13 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.053).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.294-6939A>G		intron_variant	Intron 1 of 4	ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324323.2	c.-333A>G		5_prime_UTR_variant	Exon 2 of 6		NP_001311252.1
SRD5A1	NM_001324322.2	c.319+11034A>G		intron_variant	Intron 1 of 3		NP_001311251.1
SRD5A1	NR_136739.2	n.431-6939A>G		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.294-6939A>G		intron_variant	Intron 1 of 4	1	NM_001047.4	ENSP00000274192.5

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85737 AN: 151664 Hom.: 24747 Cov.: 31

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.553

GnomAD2 exomes AF: 0.531 AC: 68115 AN: 128288 AF XY: 0.525

Gnomad AFR exome AF: 0.678

Gnomad AMR exome AF: 0.615

Gnomad ASJ exome AF: 0.532

Gnomad EAS exome AF: 0.402

Gnomad FIN exome AF: 0.536

Gnomad NFE exome AF: 0.516

Gnomad OTH exome AF: 0.532

GnomAD4 exome AF: 0.521 AC: 158419 AN: 303828 Hom.: 42025 Cov.: 0 AF XY: 0.516 AC XY: 89248 AN XY: 172994

African (AFR) AF: 0.673 AC: 5799 AN: 8622

American (AMR) AF: 0.616 AC: 16810 AN: 27272

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 5732 AN: 10782

East Asian (EAS) AF: 0.406 AC: 3737 AN: 9204

South Asian (SAS) AF: 0.486 AC: 29038 AN: 59730

European-Finnish (FIN) AF: 0.541 AC: 6683 AN: 12362

Middle Eastern (MID) AF: 0.498 AC: 1385 AN: 2780

European-Non Finnish (NFE) AF: 0.515 AC: 81830 AN: 158856

Other (OTH) AF: 0.521 AC: 7405 AN: 14220

GnomAD4 genome AF: 0.565 AC: 85805 AN: 151782 Hom.: 24760 Cov.: 31 AF XY: 0.563 AC XY: 41731 AN XY: 74136

African (AFR) AF: 0.670 AC: 27704 AN: 41374

American (AMR) AF: 0.593 AC: 9047 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1831 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2114 AN: 5138

South Asian (SAS) AF: 0.482 AC: 2314 AN: 4796

European-Finnish (FIN) AF: 0.546 AC: 5738 AN: 10508

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35135 AN: 67942

Other (OTH) AF: 0.553 AC: 1163 AN: 2104

Alfa AF: 0.547 Hom.: 15379

Bravo AF: 0.575

Asia WGS AF: 0.505 AC: 1757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.63
PhyloP100		0.43
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: rs248805; hg19: chr5-6645016; COSMIC: COSV57014068;