rs566351

Variant names:

• chr11-101114283-C-T
• rs566351
• NM_000926.4:c.1789+11724G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1789+11724G>A		intron_variant	Intron 2 of 7	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.1789+11724G>A		intron_variant	Intron 2 of 7	1	NM_000926.4	ENSP00000325120.5

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

African (AFR) AF: 0.519 AC: 21481 AN: 41416

American (AMR) AF: 0.561 AC: 8563 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2242 AN: 3468

East Asian (EAS) AF: 0.212 AC: 1093 AN: 5158

South Asian (SAS) AF: 0.343 AC: 1651 AN: 4814

European-Finnish (FIN) AF: 0.640 AC: 6729 AN: 10516

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43244 AN: 67956

Other (OTH) AF: 0.567 AC: 1198 AN: 2114

Alfa AF: 0.520 Hom.: 2173

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
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs566351; hg19: chr11-100985014;