11-101127892-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000926.4(PGR):​c.1179C>A​(p.Gly393Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,356 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=-0.003 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1179C>A	p.Gly393Gly	synonymous_variant	Exon 1 of 8	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.1179C>A	p.Gly393Gly	synonymous_variant	Exon 1 of 8	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449356 Hom.: 0 Cov.: 45 AF XY: 0.00000139 AC XY: 1 AN XY: 721470

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33022

American (AMR) AF: 0.00 AC: 0 AN: 44046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25692

East Asian (EAS) AF: 0.00 AC: 0 AN: 39044

South Asian (SAS) AF: 0.00 AC: 0 AN: 86108

European-Finnish (FIN) AF: 0.0000207 AC: 1 AN: 48352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107690

Other (OTH) AF: 0.00 AC: 0 AN: 59662

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2908

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.3
DANN	Benign	0.90
PhyloP100		-0.0030

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: rs1379130; hg19: chr11-100998623;