rs248793

Variant names:

• chr5-6633666-C-G
• rs248793
• NM_001047.4:c.90C>G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001047.4(SRD5A1):​c.90C>G​(p.Arg30Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,579,142 control chromosomes in the GnomAD database, including 239,443 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25380 hom., cov: 35)
  • Exomes 𝑓: 0.55 (214063 hom.)
• Consequence: SRD5A1 NM_001047.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.446
• Publications: 25 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.048).
• BP6: Variant 5-6633666-C-G is Benign according to our data. Variant chr5-6633666-C-G is described in ClinVar as Benign. ClinVar VariationId is 1255175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.446 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.90C>G	p.Arg30Arg	synonymous_variant	Exon 1 of 5	ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.116C>G	p.Ala39Gly	missense_variant	Exon 1 of 4		NP_001311251.1
SRD5A1	NR_136739.2	n.227C>G		non_coding_transcript_exon_variant	Exon 1 of 6
SRD5A1	NM_001324323.2	c.-632C>G		5_prime_UTR_variant	Exon 1 of 6		NP_001311252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.90C>G	p.Arg30Arg	synonymous_variant	Exon 1 of 5	1	NM_001047.4	ENSP00000274192.5
SRD5A1	ENST00000504286.2	n.90C>G		non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000518753.1
SRD5A1	ENST00000510531.6	n.90C>G		non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000425330.1
SRD5A1	ENST00000513117.1	n.90C>G		non_coding_transcript_exon_variant	Exon 1 of 4	2		ENSP00000421342.1

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87183 AN: 151970 Hom.: 25361 Cov.: 35

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.566

GnomAD2 exomes AF: 0.547 AC: 104315 AN: 190608 AF XY: 0.543

Gnomad AFR exome AF: 0.652

Gnomad AMR exome AF: 0.622

Gnomad ASJ exome AF: 0.544

Gnomad EAS exome AF: 0.405

Gnomad FIN exome AF: 0.555

Gnomad NFE exome AF: 0.542

Gnomad OTH exome AF: 0.554

GnomAD4 exome AF: 0.546 AC: 779586 AN: 1427056 Hom.: 214063 Cov.: 68 AF XY: 0.545 AC XY: 385981 AN XY: 708792

African (AFR) AF: 0.651 AC: 21400 AN: 32882

American (AMR) AF: 0.619 AC: 25851 AN: 41738

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 13964 AN: 25780

East Asian (EAS) AF: 0.410 AC: 15823 AN: 38582

South Asian (SAS) AF: 0.516 AC: 43627 AN: 84626

European-Finnish (FIN) AF: 0.560 AC: 20097 AN: 35894

Middle Eastern (MID) AF: 0.526 AC: 3001 AN: 5708

European-Non Finnish (NFE) AF: 0.547 AC: 603441 AN: 1102446

Other (OTH) AF: 0.545 AC: 32382 AN: 59400

GnomAD4 genome AF: 0.574 AC: 87258 AN: 152086 Hom.: 25380 Cov.: 35 AF XY: 0.571 AC XY: 42462 AN XY: 74372

African (AFR) AF: 0.645 AC: 26769 AN: 41508

American (AMR) AF: 0.597 AC: 9125 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1875 AN: 3466

East Asian (EAS) AF: 0.410 AC: 2112 AN: 5148

South Asian (SAS) AF: 0.509 AC: 2454 AN: 4824

European-Finnish (FIN) AF: 0.560 AC: 5933 AN: 10594

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.545 AC: 37014 AN: 67936

Other (OTH) AF: 0.566 AC: 1196 AN: 2114

Alfa AF: 0.554 Hom.: 4331

Bravo AF: 0.582

Asia WGS AF: 0.513 AC: 1782 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.0
DANN	Benign	0.66
PhyloP100		0.45
PromoterAI		-0.027	Neutral
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: rs248793; hg19: chr5-6633779; COSMIC: COSV52952592; COSMIC: COSV52952592;