rs506487

Variant names:

• chr11-101124978-C-T
• rs506487
• NM_000926.4:c.1789+1029G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 BA1

The NM_000926.4(PGR):​c.1789+1029G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,720 control chromosomes in the GnomAD database, including 5,714 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 0.25 (5714 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• 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 -7 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000926.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	NM_000926.4	MANE Select	c.1789+1029G>A		intron	N/A	NP_000917.3
	PGR	NM_001202474.3		c.1297+1029G>A		intron	N/A	NP_001189403.1
	PGR	NM_001271161.2		c.1297+1029G>A		intron	N/A	NP_001258090.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	ENST00000325455.10	TSL:1 MANE Select	c.1789+1029G>A		intron	N/A	ENSP00000325120.5
	PGR	ENST00000263463.9	TSL:1	c.1789+1029G>A		intron	N/A	ENSP00000263463.5
	PGR	ENST00000526300.5	TSL:1	n.1789+1029G>A		intron	N/A	ENSP00000436803.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38094 AN: 151600 Hom.: 5717 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.00582

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.251 AC: 38095 AN: 151720 Hom.: 5714 Cov.: 32 AF XY: 0.252 AC XY: 18691 AN XY: 74096

African (AFR) AF: 0.105 AC: 4330 AN: 41410

American (AMR) AF: 0.248 AC: 3782 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 768 AN: 3462

East Asian (EAS) AF: 0.00583 AC: 30 AN: 5144

South Asian (SAS) AF: 0.196 AC: 945 AN: 4818

European-Finnish (FIN) AF: 0.379 AC: 3964 AN: 10466

Middle Eastern (MID) AF: 0.293 AC: 85 AN: 290

European-Non Finnish (NFE) AF: 0.345 AC: 23420 AN: 67868

Other (OTH) AF: 0.246 AC: 518 AN: 2106

Alfa AF: 0.287 Hom.: 897

Bravo AF: 0.235

Asia WGS AF: 0.105 AC: 366 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Pathogenic	33
DANN	Benign	0.23
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.67		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.66		Position offset: 29
DS_DG_spliceai		0.67		Position offset: 4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs506487; hg19: chr11-100995709;