rs11571215

chr11-101063200-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.1907-448A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0291 in 153,130 control chromosomes in the GnomAD database, including 171 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 0.029 (171 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (0 hom.)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGR	NM_000926.4	c.1907-448A>G		intron_variant		ENST00000325455.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGR	ENST00000325455.10	c.1907-448A>G		intron_variant		1	NM_000926.4	P1

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4427 AN: 152176 Hom.: 170 Cov.: 32

Gnomad AFR AF: 0.0912

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0193

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0235

Gnomad SAS AF: 0.0217

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.0258

GnomAD4 exome AF: 0.00359 AC: 3 AN: 836 Hom.: 0 Cov.: 0 AF XY: 0.00429 AC XY: 2 AN XY: 466

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0132

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0455

Gnomad4 SAS exome AF: 0.0185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0293 AC: 4456 AN: 152294 Hom.: 171 Cov.: 32 AF XY: 0.0282 AC XY: 2103 AN XY: 74482

Gnomad4 AFR AF: 0.0915

Gnomad4 AMR AF: 0.0193

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0235

Gnomad4 SAS AF: 0.0217

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000941

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0123 Hom.: 14

Bravo AF: 0.0328

Asia WGS AF: 0.0470 AC: 162 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.2
Dann	Benign	0.38

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: rs11571215; hg19: chr11-100933931;