rs499699

chr11-101039401-T-C

Variant summary

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

The NM_000926.4(PGR):c.2647-130A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 700,522 control chromosomes in the GnomAD database, including 25,040 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 0.32 (8979 hom., cov: 32)
  • Exomes 𝑓: 0.23 (16061 hom.)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGR	NM_000926.4	c.2647-130A>G		intron_variant		ENST00000325455.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGR	ENST00000325455.10	c.2647-130A>G		intron_variant		1	NM_000926.4	P1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48573 AN: 151628 Hom.: 8951 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.230 AC: 125960 AN: 548776 Hom.: 16061 AF XY: 0.224 AC XY: 65581 AN XY: 293302

Gnomad4 AFR exome AF: 0.514

Gnomad4 AMR exome AF: 0.258

Gnomad4 ASJ exome AF: 0.376

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.321 AC: 48665 AN: 151746 Hom.: 8979 Cov.: 32 AF XY: 0.314 AC XY: 23302 AN XY: 74156

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.320

Alfa AF: 0.286 Hom.: 885

Bravo AF: 0.337

Asia WGS AF: 0.199 AC: 694 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.4
Dann	Benign	0.61

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: rs499699; hg19: chr11-100910132; COSMIC: COSV54802512; COSMIC: COSV54802512;