rs1870019

Positions:

• chr11-101030742-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.*8374T>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 0.224 in 205,830 control chromosomes in the GnomAD database, including 6,382 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 0.22 (4658 hom., cov: 32)
  • Exomes 𝑓: 0.23 (1724 hom.)
• Consequence: PGR NM_000926.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGR	NM_000926.4	c.*8374T>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.*8374T>C		3_prime_UTR_variant	8/8	1	NM_000926.4	ENSP00000325120	P1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33851 AN: 152026 Hom.: 4660 Cov.: 32

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.229 AC: 12308 AN: 53686 Hom.: 1724 Cov.: 0 AF XY: 0.234 AC XY: 5836 AN XY: 24906

Gnomad4 AFR exome AF: 0.0711

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.000240

Gnomad4 SAS exome AF: 0.177

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.296

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.222 AC: 33851 AN: 152144 Hom.: 4658 Cov.: 32 AF XY: 0.223 AC XY: 16584 AN XY: 74362

Gnomad4 AFR AF: 0.0723

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.00444

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.230

Alfa AF: 0.277 Hom.: 1286

Bravo AF: 0.206

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.55

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: rs1870019; hg19: chr11-100901473; COSMIC: COSV57672248;