rs1379130

Variant names:

• chr11-101127892-G-A
• rs1379130
• NM_000926.4:c.1179C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-101127892-G-A
• chr11-101127892-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.1179C>T​(p.Gly393Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,599,908 control chromosomes in the GnomAD database, including 80,947 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 (5660 hom., cov: 32)
  • Exomes 𝑓: 0.31 (75287 hom.)
• Consequence: PGR NM_000926.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 17 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]

PGR-AS1 (HGNC:52650): (PGR antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.003 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 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.1179C>T	p.Gly393Gly	synonymous	Exon 1 of 8	NP_000917.3
	PGR	NM_001202474.3		c.687C>T	p.Gly229Gly	synonymous	Exon 1 of 8	NP_001189403.1
	PGR	NM_001271161.2		c.687C>T	p.Gly229Gly	synonymous	Exon 1 of 7	NP_001258090.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	ENST00000325455.10	TSL:1 MANE Select	c.1179C>T	p.Gly393Gly	synonymous	Exon 1 of 8	ENSP00000325120.5
	PGR	ENST00000263463.9	TSL:1	c.1179C>T	p.Gly393Gly	synonymous	Exon 1 of 7	ENSP00000263463.5
	PGR	ENST00000526300.5	TSL:1	n.1179C>T		non_coding_transcript_exon	Exon 1 of 6	ENSP00000436803.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37007 AN: 150556 Hom.: 5661 Cov.: 32

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.00615

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.250

GnomAD2 exomes AF: 0.268 AC: 61341 AN: 229144 AF XY: 0.273

Gnomad AFR exome AF: 0.0757

Gnomad AMR exome AF: 0.229

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.00541

Gnomad FIN exome AF: 0.388

Gnomad NFE exome AF: 0.348

Gnomad OTH exome AF: 0.297

GnomAD4 exome AF: 0.313 AC: 453563 AN: 1449230 Hom.: 75287 Cov.: 45 AF XY: 0.311 AC XY: 224497 AN XY: 721396

African (AFR) AF: 0.0702 AC: 2319 AN: 33020

American (AMR) AF: 0.236 AC: 10389 AN: 44030

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 5808 AN: 25690

East Asian (EAS) AF: 0.00236 AC: 92 AN: 39042

South Asian (SAS) AF: 0.216 AC: 18635 AN: 86098

European-Finnish (FIN) AF: 0.382 AC: 18436 AN: 48298

Middle Eastern (MID) AF: 0.308 AC: 1768 AN: 5740

European-Non Finnish (NFE) AF: 0.343 AC: 379602 AN: 1107656

Other (OTH) AF: 0.277 AC: 16514 AN: 59656

GnomAD4 genome AF: 0.246 AC: 37003 AN: 150678 Hom.: 5660 Cov.: 32 AF XY: 0.248 AC XY: 18228 AN XY: 73634

African (AFR) AF: 0.0777 AC: 3189 AN: 41048

American (AMR) AF: 0.248 AC: 3765 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 742 AN: 3458

East Asian (EAS) AF: 0.00617 AC: 30 AN: 4864

South Asian (SAS) AF: 0.199 AC: 940 AN: 4716

European-Finnish (FIN) AF: 0.385 AC: 4042 AN: 10496

Middle Eastern (MID) AF: 0.303 AC: 86 AN: 284

European-Non Finnish (NFE) AF: 0.347 AC: 23441 AN: 67616

Other (OTH) AF: 0.246 AC: 514 AN: 2090

Alfa AF: 0.289 Hom.: 2908

Bravo AF: 0.226

Asia WGS AF: 0.104 AC: 363 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.95
PhyloP100		-0.0030
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1379130; hg19: chr11-100998623; COSMIC: COSV108004167; COSMIC: COSV108004167;