rs511484

Variant names:

• chr11-101047702-G-C
• rs511484
• NM_000926.4:c.2488+2227C>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.2488+2227C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 151,998 control chromosomes in the GnomAD database, including 5,816 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 0.27 (5816 hom., cov: 31)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.781
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	NM_000926.4	MANE Select	c.2488+2227C>G		intron	N/A	NP_000917.3	P06401-1
	PGR	NM_001202474.3		c.1996+2227C>G		intron	N/A	NP_001189403.1	P06401-2
	PGR	NM_001271161.2		c.1690+2227C>G		intron	N/A	NP_001258090.1	P06401

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	ENST00000325455.10	TSL:1 MANE Select	c.2488+2227C>G		intron	N/A	ENSP00000325120.5	P06401-1
	PGR	ENST00000263463.9	TSL:1	c.2182+2227C>G		intron	N/A	ENSP00000263463.5	P06401-5
	PGR	ENST00000526300.5	TSL:1	n.2051+3722C>G		intron	N/A	ENSP00000436803.1	Q8NG45

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41192 AN: 151880 Hom.: 5793 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.272 AC: 41276 AN: 151998 Hom.: 5816 Cov.: 31 AF XY: 0.266 AC XY: 19767 AN XY: 74280

African (AFR) AF: 0.350 AC: 14505 AN: 41446

American (AMR) AF: 0.281 AC: 4292 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1343 AN: 3472

East Asian (EAS) AF: 0.226 AC: 1161 AN: 5146

South Asian (SAS) AF: 0.128 AC: 614 AN: 4808

European-Finnish (FIN) AF: 0.216 AC: 2285 AN: 10562

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16161 AN: 67990

Other (OTH) AF: 0.285 AC: 601 AN: 2110

Alfa AF: 0.256 Hom.: 735

Bravo AF: 0.282

Asia WGS AF: 0.192 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.89
DANN	Benign	0.39
PhyloP100		-0.78
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: rs511484; hg19: chr11-100918433;