rs555653

Variant names:

• chr11-101098814-A-G
• rs555653
• NM_000926.4:c.1790-6938T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000926.4(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 NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.605
• Publications: 8 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1790-6938T>C		intron_variant	Intron 2 of 7	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.1790-6938T>C		intron_variant	Intron 2 of 7	1	NM_000926.4	ENSP00000325120.5

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

African (AFR) AF: 0.414 AC: 17180 AN: 41482

American (AMR) AF: 0.420 AC: 6416 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2023 AN: 3472

East Asian (EAS) AF: 0.206 AC: 1070 AN: 5184

South Asian (SAS) AF: 0.340 AC: 1638 AN: 4824

European-Finnish (FIN) AF: 0.416 AC: 4398 AN: 10574

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32255 AN: 67966

Other (OTH) AF: 0.446 AC: 943 AN: 2112

Alfa AF: 0.461 Hom.: 47930

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
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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: rs555653; hg19: chr11-100969545;