rs566351

chr11-101114283-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.1789+11724G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,910 control chromosomes in the GnomAD database, including 25,639 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 0.57 (25639 hom., cov: 31)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGR	NM_000926.4	c.1789+11724G>A		intron_variant		ENST00000325455.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGR	ENST00000325455.10	c.1789+11724G>A		intron_variant		1	NM_000926.4	P1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86870 AN: 151790 Hom.: 25608 Cov.: 31

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.572 AC: 86950 AN: 151910 Hom.: 25639 Cov.: 31 AF XY: 0.567 AC XY: 42069 AN XY: 74228

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.567

Alfa AF: 0.518 Hom.: 2057

Bravo AF: 0.566

Asia WGS AF: 0.301 AC: 1048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.5
Dann	Benign	0.74

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: rs566351; hg19: chr11-100985014;