5-6666989-C-T

Position:

• chr5-6666989-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001047.4(SRD5A1):​c.714-1213C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,242 control chromosomes in the GnomAD database, including 4,816 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 0.24 (4816 hom., cov: 33)
• Consequence: SRD5A1 NM_001047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.714-1213C>T		intron_variant		ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.573-1213C>T		intron_variant			NP_001311251.1
SRD5A1	NM_001324323.2	c.495-1213C>T		intron_variant			NP_001311252.1
SRD5A1	NR_136739.2	n.1041-1213C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.714-1213C>T		intron_variant		1	NM_001047.4	ENSP00000274192.5
SRD5A1	ENST00000510531.5	n.*835-1213C>T		intron_variant		2		ENSP00000425330.1
SRD5A1	ENST00000513117.1	n.*139-1213C>T		intron_variant		2		ENSP00000421342.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36727 AN: 152124 Hom.: 4817 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.0171

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.241 AC: 36751 AN: 152242 Hom.: 4816 Cov.: 33 AF XY: 0.234 AC XY: 17450 AN XY: 74446

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.0168

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.271

Alfa AF: 0.279 Hom.: 8132

Bravo AF: 0.246

Asia WGS AF: 0.109 AC: 381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.50

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: rs6872996; hg19: chr5-6667102;