rs1042839

Positions:

• chr11-101051471-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000926.4(PGR):​c.2310C>T​(p.His770His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,604,830 control chromosomes in the GnomAD database, including 18,615 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 0.11 (1295 hom., cov: 33)
  • Exomes 𝑓: 0.15 (17320 hom.)
• Consequence: PGR NM_000926.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.750

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]

PGR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=0.75 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGR	NM_000926.4	c.2310C>T	p.His770His	synonymous_variant	5/8	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.2310C>T	p.His770His	synonymous_variant	5/8	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17403 AN: 151936 Hom.: 1296 Cov.: 33

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.0694

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.132

GnomAD3 exomes AF: 0.129 AC: 32181 AN: 250432 Hom.: 2511 AF XY: 0.129 AC XY: 17425 AN XY: 135316

Gnomad AFR exome AF: 0.0267

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.246

Gnomad EAS exome AF: 0.0109

Gnomad SAS exome AF: 0.0771

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.148 AC: 215098 AN: 1452776 Hom.: 17320 Cov.: 29 AF XY: 0.146 AC XY: 105450 AN XY: 723220

Gnomad4 AFR exome AF: 0.0226

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.0100

Gnomad4 SAS exome AF: 0.0773

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.114 AC: 17403 AN: 152054 Hom.: 1295 Cov.: 33 AF XY: 0.112 AC XY: 8347 AN XY: 74294

Gnomad4 AFR AF: 0.0299

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.0692

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.131

Alfa AF: 0.148 Hom.: 1556

Bravo AF: 0.110

Asia WGS AF: 0.0520 AC: 183 AN: 3478

EpiCase AF: 0.162

EpiControl AF: 0.157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.9
DANN	Benign	0.42

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: rs1042839; hg19: chr11-100922202;