rs1042839

Variant names:

• chr11-101051471-G-A
• rs1042839
• NM_000926.4:c.2310C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-101051471-G-A
• chr11-101051471-G-T

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.2310C>T​(p.His770His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,604,830 control chromosomes in the GnomAD database, including 18,615 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 0.11 (1295 hom., cov: 33)
  • Exomes 𝑓: 0.15 (17320 hom.)
• Consequence: PGR NM_000926.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.750
• Publications: 55 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=-0.49).
• BP7: Synonymous conserved (PhyloP=0.75 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 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.2310C>T	p.His770His	synonymous	Exon 5 of 8	NP_000917.3	P06401-1
	PGR	NM_001202474.3		c.1818C>T	p.His606His	synonymous	Exon 5 of 8	NP_001189403.1	P06401-2
	PGR	NM_001271161.2		c.1512C>T	p.His504His	synonymous	Exon 4 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.2310C>T	p.His770His	synonymous	Exon 5 of 8	ENSP00000325120.5	P06401-1
	PGR	ENST00000263463.9	TSL:1	c.2004C>T	p.His668His	synonymous	Exon 4 of 7	ENSP00000263463.5	P06401-5
	PGR	ENST00000526300.5	TSL:1	n.2004C>T		non_coding_transcript_exon	Exon 4 of 6	ENSP00000436803.1	Q8NG45

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17403 AN: 151936 Hom.: 1296 Cov.: 33

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.0694

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.132

GnomAD2 exomes AF: 0.129 AC: 32181 AN: 250432 AF XY: 0.129

Gnomad AFR exome AF: 0.0267

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.246

Gnomad EAS exome AF: 0.0109

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.148 AC: 215098 AN: 1452776 Hom.: 17320 Cov.: 29 AF XY: 0.146 AC XY: 105450 AN XY: 723220

African (AFR) AF: 0.0226 AC: 753 AN: 33362

American (AMR) AF: 0.144 AC: 6429 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 6383 AN: 26032

East Asian (EAS) AF: 0.0100 AC: 396 AN: 39614

South Asian (SAS) AF: 0.0773 AC: 6651 AN: 86082

European-Finnish (FIN) AF: 0.150 AC: 8006 AN: 53394

Middle Eastern (MID) AF: 0.117 AC: 658 AN: 5618

European-Non Finnish (NFE) AF: 0.160 AC: 177033 AN: 1103944

Other (OTH) AF: 0.146 AC: 8789 AN: 60076

GnomAD4 genome AF: 0.114 AC: 17403 AN: 152054 Hom.: 1295 Cov.: 33 AF XY: 0.112 AC XY: 8347 AN XY: 74294

African (AFR) AF: 0.0299 AC: 1243 AN: 41532

American (AMR) AF: 0.135 AC: 2062 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 863 AN: 3468

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5178

South Asian (SAS) AF: 0.0692 AC: 334 AN: 4826

European-Finnish (FIN) AF: 0.150 AC: 1584 AN: 10528

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.158 AC: 10768 AN: 67970

Other (OTH) AF: 0.131 AC: 277 AN: 2108

Alfa AF: 0.148 Hom.: 1911

Bravo AF: 0.110

Asia WGS AF: 0.0520 AC: 183 AN: 3478

EpiCase AF: 0.162

EpiControl AF: 0.157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.9
DANN	Benign	0.42
PhyloP100		0.75
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: rs1042839; hg19: chr11-100922202;