rs484389

Positions:

• chr11-101039078-A-G

Variant summary

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

The NM_000926.4(PGR):​c.*38T>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 0.243 in 1,551,512 control chromosomes in the GnomAD database, including 47,866 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 0.28 (6474 hom., cov: 32)
  • Exomes 𝑓: 0.24 (41392 hom.)
• Consequence: PGR NM_000926.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

Genes affected

PGR (HGNC:8910): (progesterone receptor) This gene encodes a member of the steroid receptor superfamily. The encoded protein mediates the physiological effects of progesterone, which plays a central role in reproductive events associated with the establishment and maintenance of pregnancy. This gene uses two distinct promotors and translation start sites in the first exon to produce several transcript variants, both protein coding and non-protein coding. Two of the isoforms (A and B) are identical except for an additional 165 amino acids found in the N-terminus of isoform B and mediate their own response genes and physiologic effects with little overlap. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGR	NM_000926.4	c.*38T>C		3_prime_UTR_variant	8/8	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.*38T>C		3_prime_UTR_variant	8/8	1	NM_000926.4	ENSP00000325120	P1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 42987 AN: 151562 Hom.: 6455 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.293

GnomAD3 exomes AF: 0.241 AC: 59220 AN: 246110 Hom.: 7681 AF XY: 0.232 AC XY: 31020 AN XY: 133672

Gnomad AFR exome AF: 0.385

Gnomad AMR exome AF: 0.266

Gnomad ASJ exome AF: 0.383

Gnomad EAS exome AF: 0.223

Gnomad SAS exome AF: 0.128

Gnomad FIN exome AF: 0.225

Gnomad NFE exome AF: 0.236

Gnomad OTH exome AF: 0.258

GnomAD4 exome AF: 0.238 AC: 333808 AN: 1399832 Hom.: 41392 Cov.: 23 AF XY: 0.234 AC XY: 163977 AN XY: 699824

Gnomad4 AFR exome AF: 0.386

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.379

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.259

GnomAD4 genome AF: 0.284 AC: 43068 AN: 151680 Hom.: 6474 Cov.: 32 AF XY: 0.278 AC XY: 20616 AN XY: 74166

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.294

Alfa AF: 0.259 Hom.: 5278

Bravo AF: 0.296

Asia WGS AF: 0.192 AC: 668 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.4
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs484389; hg19: chr11-100909809; COSMIC: COSV54809145; COSMIC: COSV54809145;