rs542384

Variant names:

• chr11-101095907-T-A
• rs542384
• NM_000926.4:c.1790-4031A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-101095907-T-A
• chr11-101095907-T-G

Variant summary

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

The NM_000926.4(PGR):​c.1790-4031A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,068 control chromosomes in the GnomAD database, including 40,472 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 0.71 (40472 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1790-4031A>T		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.1790-4031A>T		intron_variant	Intron 2 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108572 AN: 151950 Hom.: 40446 Cov.: 32

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.714 AC: 108641 AN: 152068 Hom.: 40472 Cov.: 32 AF XY: 0.707 AC XY: 52604 AN XY: 74354

African (AFR) AF: 0.593 AC: 24581 AN: 41456

American (AMR) AF: 0.682 AC: 10411 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2824 AN: 3472

East Asian (EAS) AF: 0.211 AC: 1090 AN: 5160

South Asian (SAS) AF: 0.543 AC: 2620 AN: 4822

European-Finnish (FIN) AF: 0.796 AC: 8429 AN: 10584

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.827 AC: 56243 AN: 67986

Other (OTH) AF: 0.710 AC: 1500 AN: 2112

Alfa AF: 0.731 Hom.: 2654

Bravo AF: 0.700

Asia WGS AF: 0.374 AC: 1304 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.6
DANN	Benign	0.63
PhyloP100		0.22
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: rs542384; hg19: chr11-100966638;