rs516693

chr11-101093012-C-T

Variant summary

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

The NM_000926.4(PGR):c.1790-1136G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,028 control chromosomes in the GnomAD database, including 2,439 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 0.17 (2439 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGR	NM_000926.4	c.1790-1136G>A		intron_variant		ENST00000325455.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGR	ENST00000325455.10	c.1790-1136G>A		intron_variant		1	NM_000926.4	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25179 AN: 151910 Hom.: 2418 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.0637

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.166 AC: 25250 AN: 152028 Hom.: 2439 Cov.: 32 AF XY: 0.163 AC XY: 12144 AN XY: 74312

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.0648

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.156

Alfa AF: 0.130 Hom.: 568

Bravo AF: 0.175

Asia WGS AF: 0.129 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.024
Dann	Benign	0.41

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: rs516693; hg19: chr11-100963743;