rs555653

Positions:

• chr11-101098814-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000325455.10(PGR):​c.1790-6938T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 152,106 control chromosomes in the GnomAD database, including 14,872 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 0.44 (14872 hom., cov: 33)
• Consequence: PGR ENST00000325455.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.605

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGR	NM_000926.4	c.1790-6938T>C		intron_variant		ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.1790-6938T>C		intron_variant		1	NM_000926.4	ENSP00000325120	P1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66460 AN: 151988 Hom.: 14853 Cov.: 33

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.448

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.437 AC: 66522 AN: 152106 Hom.: 14872 Cov.: 33 AF XY: 0.430 AC XY: 31985 AN XY: 74362

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.446

Alfa AF: 0.468 Hom.: 22730

Bravo AF: 0.436

Asia WGS AF: 0.264 AC: 920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs555653; hg19: chr11-100969545;