rs1379130

Positions:

• chr11-101127892-G-A
• chr11-101127892-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_000926.4(PGR):​c.1179C>T​(p.Gly393=) 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 11-101127892-G-A is Benign according to our data. Variant chr11-101127892-G-A is described in Lovd as [Benign].
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGR	NM_000926.4	c.1179C>T	p.Gly393=	synonymous_variant	1/8	ENST00000325455.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGR	ENST00000325455.10	c.1179C>T	p.Gly393=	synonymous_variant	1/8	1	NM_000926.4	P1

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

GnomAD3 exomes AF: 0.268 AC: 61341 AN: 229144 Hom.: 9651 AF XY: 0.273 AC XY: 34645 AN XY: 127102

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 SAS exome AF: 0.215

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

Gnomad4 AFR exome AF: 0.0702

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.226

Gnomad4 EAS exome AF: 0.00236

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.382

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.277

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

Gnomad4 AFR AF: 0.0777

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.00617

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.246

Alfa AF: 0.292 Hom.: 2905

Bravo AF: 0.226

Asia WGS AF: 0.104 AC: 363 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.95

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

Publications

LitVar

Other links and lift over

dbSNP: rs1379130; hg19: chr11-100998623;