chr11-101049844-A-T

Position:

• chr11-101049844-A-T

Variant summary

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

The NM_000926.4(PGR):​c.2488+85T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,080,746 control chromosomes in the GnomAD database, including 33,286 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 0.27 (5799 hom., cov: 32)
  • Exomes 𝑓: 0.24 (27487 hom.)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGR	NM_000926.4	c.2488+85T>A		intron_variant		ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.2488+85T>A		intron_variant		1	NM_000926.4	ENSP00000325120	P1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41132 AN: 151966 Hom.: 5776 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.239 AC: 221669 AN: 928662 Hom.: 27487 AF XY: 0.234 AC XY: 113093 AN XY: 483828

Gnomad4 AFR exome AF: 0.344

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.380

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.260

GnomAD4 genome AF: 0.271 AC: 41216 AN: 152084 Hom.: 5799 Cov.: 32 AF XY: 0.266 AC XY: 19748 AN XY: 74320

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.284

Alfa AF: 0.147 Hom.: 257

Bravo AF: 0.282

Asia WGS AF: 0.191 AC: 665 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.68

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: rs526487; hg19: chr11-100920575; COSMIC: COSV54813326; COSMIC: COSV54813326;