chr11-101039260-T-C

Variant names:

• chr11-101039260-T-C
• rs500760
• NM_000926.4:c.2658A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000926.4(PGR):​c.2658A>G​(p.Gln886Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,604,620 control chromosomes in the GnomAD database, including 49,998 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 0.28 (6467 hom., cov: 32)
  • Exomes 𝑓: 0.24 (43531 hom.)
• Consequence: PGR NM_000926.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518
• Publications: 42 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=-0.518 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 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.2658A>G	p.Gln886Gln	synonymous	Exon 8 of 8	NP_000917.3	P06401-1
	PGR	NM_001202474.3		c.2166A>G	p.Gln722Gln	synonymous	Exon 8 of 8	NP_001189403.1	P06401-2
	PGR	NM_001271161.2		c.1860A>G	p.Gln620Gln	synonymous	Exon 7 of 7	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.2658A>G	p.Gln886Gln	synonymous	Exon 8 of 8	ENSP00000325120.5	P06401-1
	PGR	ENST00000263463.9	TSL:1	c.2352A>G	p.Gln784Gln	synonymous	Exon 7 of 7	ENSP00000263463.5	P06401-5
	PGR	ENST00000526300.5	TSL:1	n.*133A>G		non_coding_transcript_exon	Exon 6 of 6	ENSP00000436803.1	Q8NG45

Frequencies

GnomAD3 genomes AF: 0.284 AC: 42999 AN: 151652 Hom.: 6448 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.293

GnomAD2 exomes AF: 0.241 AC: 60377 AN: 250118 AF XY: 0.233

Gnomad AFR exome AF: 0.386

Gnomad AMR exome AF: 0.266

Gnomad ASJ exome AF: 0.384

Gnomad EAS exome AF: 0.223

Gnomad FIN exome AF: 0.224

Gnomad NFE exome AF: 0.236

Gnomad OTH exome AF: 0.258

GnomAD4 exome AF: 0.240 AC: 348580 AN: 1452850 Hom.: 43531 Cov.: 30 AF XY: 0.236 AC XY: 170514 AN XY: 723172

African (AFR) AF: 0.388 AC: 12879 AN: 33188

American (AMR) AF: 0.264 AC: 11754 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 9884 AN: 26016

East Asian (EAS) AF: 0.221 AC: 8731 AN: 39498

South Asian (SAS) AF: 0.129 AC: 11130 AN: 86072

European-Finnish (FIN) AF: 0.223 AC: 11900 AN: 53326

Middle Eastern (MID) AF: 0.235 AC: 1349 AN: 5744

European-Non Finnish (NFE) AF: 0.240 AC: 265380 AN: 1104444

Other (OTH) AF: 0.260 AC: 15573 AN: 60002

GnomAD4 genome AF: 0.284 AC: 43080 AN: 151770 Hom.: 6467 Cov.: 32 AF XY: 0.278 AC XY: 20630 AN XY: 74226

African (AFR) AF: 0.394 AC: 16300 AN: 41408

American (AMR) AF: 0.284 AC: 4328 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1340 AN: 3468

East Asian (EAS) AF: 0.223 AC: 1152 AN: 5160

South Asian (SAS) AF: 0.128 AC: 616 AN: 4826

European-Finnish (FIN) AF: 0.216 AC: 2289 AN: 10580

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16120 AN: 67794

Other (OTH) AF: 0.294 AC: 620 AN: 2110

Alfa AF: 0.260 Hom.: 16547

Bravo AF: 0.296

Asia WGS AF: 0.193 AC: 673 AN: 3478

EpiCase AF: 0.249

EpiControl AF: 0.245

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.88
DANN	Benign	0.50
PhyloP100		-0.52
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: rs500760; hg19: chr11-100909991; COSMIC: COSV54809154; COSMIC: COSV54809154;