Genetic Variant NM_000926.4:c.1179C>T (chr11-101127892-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

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. 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00300

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
PGR	NM_000926.4 link	c.1179C>T	p.Gly393Gly	synonymous_variant	Exon 1 of 8	ENST00000325455.10	NP_000917.3	P06401-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10 link	c.1179C>T	p.Gly393Gly	synonymous_variant	Exon 1 of 8	1	NM_000926.4	ENSP00000325120.5		P06401-1

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37007

AN:

150556

Hom.:

5661

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.311

AC XY:

224497

AN XY:

721396

show subpopulations

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.:

AF XY:

0.248

AC XY:

18228

AN XY:

73634

show subpopulations

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over