rs572698

Positions:

• chr11-101041830-C-A

Variant summary

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

The NM_000926.4(PGR):​c.2646+115G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 906,620 control chromosomes in the GnomAD database, including 29,238 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 (6424 hom., cov: 32)
  • Exomes 𝑓: 0.24 (22814 hom.)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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 (AFR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGR	NM_000926.4	c.2646+115G>T		intron_variant		ENST00000325455.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGR	ENST00000325455.10	c.2646+115G>T		intron_variant		1	NM_000926.4	P1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42868 AN: 151282 Hom.: 6407 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.260

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.240 AC: 181330 AN: 755228 Hom.: 22814 Cov.: 10 AF XY: 0.234 AC XY: 92057 AN XY: 393456

Gnomad4 AFR exome AF: 0.385

Gnomad4 AMR exome AF: 0.257

Gnomad4 ASJ exome AF: 0.380

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.243

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.284 AC: 42947 AN: 151392 Hom.: 6424 Cov.: 32 AF XY: 0.278 AC XY: 20549 AN XY: 73924

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.292

Alfa AF: 0.265 Hom.: 720

Bravo AF: 0.296

Asia WGS AF: 0.193 AC: 671 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.14

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: rs572698; hg19: chr11-100912561;