rs1824126

Variant names:

• chr11-101107945-G-A
• rs1824126
• NM_000926.4:c.1790-16069C>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.1790-16069C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 150,076 control chromosomes in the GnomAD database, including 6,674 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 0.29 (6674 hom., cov: 29)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1790-16069C>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.1790-16069C>T		intron_variant	Intron 2 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.293 AC: 43891 AN: 149966 Hom.: 6655 Cov.: 29

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.293 AC: 43949 AN: 150076 Hom.: 6674 Cov.: 29 AF XY: 0.288 AC XY: 21078 AN XY: 73192

African (AFR) AF: 0.296 AC: 12062 AN: 40796

American (AMR) AF: 0.271 AC: 4080 AN: 15044

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1152 AN: 3460

East Asian (EAS) AF: 0.191 AC: 982 AN: 5140

South Asian (SAS) AF: 0.253 AC: 1201 AN: 4744

European-Finnish (FIN) AF: 0.245 AC: 2464 AN: 10070

Middle Eastern (MID) AF: 0.285 AC: 82 AN: 288

European-Non Finnish (NFE) AF: 0.312 AC: 21080 AN: 67536

Other (OTH) AF: 0.290 AC: 606 AN: 2090

Alfa AF: 0.302 Hom.: 894

Bravo AF: 0.297

Asia WGS AF: 0.198 AC: 689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.72
PhyloP100		1.6
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: rs1824126; hg19: chr11-100978676;