11-101066329-C-T

Variant names:

• chr11-101066329-C-T
• rs11224579
• NM_000926.4:c.1907-3577G>A

Variant summary

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

The NM_000926.4(PGR):​c.1907-3577G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,134 control chromosomes in the GnomAD database, including 2,937 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 0.15 (2937 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333
• Publications: 7 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 (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1907-3577G>A		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.1907-3577G>A		intron_variant	Intron 3 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22683 AN: 152016 Hom.: 2927 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.149 AC: 22709 AN: 152134 Hom.: 2937 Cov.: 32 AF XY: 0.158 AC XY: 11721 AN XY: 74368

African (AFR) AF: 0.129 AC: 5371 AN: 41526

American (AMR) AF: 0.206 AC: 3138 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3468

East Asian (EAS) AF: 0.741 AC: 3814 AN: 5144

South Asian (SAS) AF: 0.387 AC: 1866 AN: 4818

European-Finnish (FIN) AF: 0.110 AC: 1161 AN: 10600

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0957 AC: 6508 AN: 67996

Other (OTH) AF: 0.163 AC: 344 AN: 2112

Alfa AF: 0.105 Hom.: 1740

Bravo AF: 0.155

Asia WGS AF: 0.558 AC: 1935 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	5.9
DANN	Benign	0.81
PhyloP100		-0.33
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: rs11224579; hg19: chr11-100937060;