rs506487

Positions:

• chr11-101124978-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000926.4(PGR):​c.1789+1029G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,720 control chromosomes in the GnomAD database, including 5,714 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 0.25 (5714 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGR	NM_000926.4	c.1789+1029G>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.1789+1029G>A		intron_variant		1	NM_000926.4	ENSP00000325120	P1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38094 AN: 151600 Hom.: 5717 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.00582

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.250

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.251 AC: 38095 AN: 151720 Hom.: 5714 Cov.: 32 AF XY: 0.252 AC XY: 18691 AN XY: 74096

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.00583

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.246

Alfa AF: 0.294 Hom.: 892

Bravo AF: 0.235

Asia WGS AF: 0.105 AC: 366 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Pathogenic	33
DANN	Benign	0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.67		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.66		Position offset: 29
DS_DG_spliceai		0.67		Position offset: 4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs506487; hg19: chr11-100995709;