5-6656094-A-G

Position:

• chr5-6656094-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001047.4(SRD5A1):​c.477A>G​(p.Leu159Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000528 in 1,613,938 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00034 (3 hom.)
• Consequence: SRD5A1 NM_001047.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.480

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]

SRD5A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-6656094-A-G is Benign according to our data. Variant chr5-6656094-A-G is described in ClinVar as [Benign]. Clinvar id is 791132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.48 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.477A>G	p.Leu159Leu	synonymous_variant	3/5	ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.336A>G	p.Leu112Leu	synonymous_variant	2/4		NP_001311251.1
SRD5A1	NM_001324323.2	c.258A>G	p.Leu86Leu	synonymous_variant	4/6		NP_001311252.1
SRD5A1	NR_136739.2	n.804A>G		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.477A>G	p.Leu159Leu	synonymous_variant	3/5	1	NM_001047.4	ENSP00000274192.5
SRD5A1	ENST00000510531.5	n.*598A>G		non_coding_transcript_exon_variant	4/6	2		ENSP00000425330.1
SRD5A1	ENST00000513117.1	n.310A>G		non_coding_transcript_exon_variant	2/4	2		ENSP00000421342.1
SRD5A1	ENST00000510531.5	n.*598A>G		3_prime_UTR_variant	4/6	2		ENSP00000425330.1

Frequencies

GnomAD3 genomes AF: 0.00238 AC: 362 AN: 152192 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00789

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.000705 AC: 177 AN: 251172 Hom.: 0 AF XY: 0.000508 AC XY: 69 AN XY: 135778

Gnomad AFR exome AF: 0.00819

Gnomad AMR exome AF: 0.000638

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000336 AC: 491 AN: 1461628 Hom.: 3 Cov.: 29 AF XY: 0.000290 AC XY: 211 AN XY: 727112

Gnomad4 AFR exome AF: 0.00917

Gnomad4 AMR exome AF: 0.000851

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000809

Gnomad4 OTH exome AF: 0.000828

GnomAD4 genome AF: 0.00237 AC: 361 AN: 152310 Hom.: 0 Cov.: 33 AF XY: 0.00239 AC XY: 178 AN XY: 74468

Gnomad4 AFR AF: 0.00784

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00144 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 03, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.42
DANN	Benign	0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs8192208; hg19: chr5-6656207;