rs569857

Variant names:

• chr11-101052569-T-A
• rs569857
• NM_000926.4:c.2213-1001A>T

Variant summary

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

The NM_000926.4(PGR):​c.2213-1001A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 152,042 control chromosomes in the GnomAD database, including 468 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 0.075 (468 hom., cov: 31)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.2213-1001A>T		intron_variant	Intron 4 of 7	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.2213-1001A>T		intron_variant	Intron 4 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.0750 AC: 11399 AN: 151924 Hom.: 469 Cov.: 31

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.0328

Gnomad FIN AF: 0.0654

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0706

Gnomad OTH AF: 0.0903

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

GnomAD4 genome AF: 0.0751 AC: 11411 AN: 152042 Hom.: 468 Cov.: 31 AF XY: 0.0756 AC XY: 5623 AN XY: 74332

African (AFR) AF: 0.0628 AC: 2605 AN: 41484

American (AMR) AF: 0.102 AC: 1552 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 366 AN: 3462

East Asian (EAS) AF: 0.188 AC: 968 AN: 5162

South Asian (SAS) AF: 0.0333 AC: 160 AN: 4808

European-Finnish (FIN) AF: 0.0654 AC: 692 AN: 10586

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0706 AC: 4798 AN: 67972

Other (OTH) AF: 0.0898 AC: 190 AN: 2116

Alfa AF: 0.0710 Hom.: 50

Bravo AF: 0.0798

Asia WGS AF: 0.0800 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.43
PhyloP100		-0.57
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: rs569857; hg19: chr11-100923300;