rs559700

Variant names:

• chr11-101092778-T-C
• rs559700
• NM_000926.4:c.1790-902A>G

Variant summary

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

The NM_000926.4(PGR):​c.1790-902A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,250 control chromosomes in the GnomAD database, including 1,360 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 0.12 (1360 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.847
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1790-902A>G		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.1790-902A>G		intron_variant	Intron 2 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17846 AN: 152132 Hom.: 1361 Cov.: 32

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.0802

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.117 AC: 17845 AN: 152250 Hom.: 1360 Cov.: 32 AF XY: 0.115 AC XY: 8579 AN XY: 74438

African (AFR) AF: 0.0302 AC: 1256 AN: 41554

American (AMR) AF: 0.138 AC: 2103 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 866 AN: 3472

East Asian (EAS) AF: 0.0129 AC: 67 AN: 5180

South Asian (SAS) AF: 0.0799 AC: 386 AN: 4832

European-Finnish (FIN) AF: 0.157 AC: 1668 AN: 10606

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10946 AN: 68000

Other (OTH) AF: 0.133 AC: 281 AN: 2112

Alfa AF: 0.141 Hom.: 198

Bravo AF: 0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.62
PhyloP100		0.85
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: rs559700; hg19: chr11-100963509;