11-101089635-T-C

Variant names:

• chr11-101089635-T-C
• rs493220
• NM_000926.4:c.1906+2125A>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.1906+2125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 146,302 control chromosomes in the GnomAD database, including 5,631 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 0.25 (5631 hom., cov: 29)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.862
• Publications: 4 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 = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1906+2125A>G		intron_variant	Intron 3 of 7	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.1906+2125A>G		intron_variant	Intron 3 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.253 AC: 37009 AN: 146190 Hom.: 5634 Cov.: 29

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.00615

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.295

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.253 AC: 37006 AN: 146302 Hom.: 5631 Cov.: 29 AF XY: 0.256 AC XY: 18176 AN XY: 71014

African (AFR) AF: 0.0856 AC: 3319 AN: 38768

American (AMR) AF: 0.260 AC: 3727 AN: 14322

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 765 AN: 3450

East Asian (EAS) AF: 0.00616 AC: 30 AN: 4868

South Asian (SAS) AF: 0.205 AC: 966 AN: 4706

European-Finnish (FIN) AF: 0.407 AC: 3932 AN: 9656

Middle Eastern (MID) AF: 0.300 AC: 87 AN: 290

European-Non Finnish (NFE) AF: 0.348 AC: 23444 AN: 67318

Other (OTH) AF: 0.250 AC: 506 AN: 2020

Alfa AF: 0.309 Hom.: 32912

Bravo AF: 0.227

Asia WGS AF: 0.105 AC: 367 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	0.20
DANN	Benign	0.33
PhyloP100		-0.86
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: rs493220; hg19: chr11-100960366;