rs590688

Variant names:

• chr11-101105243-C-G
• rs590688
• NM_000926.4:c.1790-13367G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000926.4(PGR):​c.1790-13367G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,956 control chromosomes in the GnomAD database, including 16,458 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 0.46 (16458 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 13 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1790-13367G>C		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.1790-13367G>C		intron_variant	Intron 2 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70019 AN: 151838 Hom.: 16434 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.461 AC: 70089 AN: 151956 Hom.: 16458 Cov.: 32 AF XY: 0.453 AC XY: 33633 AN XY: 74256

African (AFR) AF: 0.485 AC: 20101 AN: 41458

American (AMR) AF: 0.432 AC: 6593 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2059 AN: 3468

East Asian (EAS) AF: 0.204 AC: 1050 AN: 5150

South Asian (SAS) AF: 0.339 AC: 1633 AN: 4812

European-Finnish (FIN) AF: 0.417 AC: 4395 AN: 10542

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32680 AN: 67938

Other (OTH) AF: 0.463 AC: 976 AN: 2108

Alfa AF: 0.474 Hom.: 2378

Bravo AF: 0.463

Asia WGS AF: 0.267 AC: 933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.087
DANN	Benign	0.43
PhyloP100		-2.1
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: rs590688; hg19: chr11-100975974; COSMIC: COSV54811532;