rs653752

Variant names:

• chr11-101077379-C-G
• rs653752
• NM_000926.4:c.1906+14381G>C

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+14381G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,972 control chromosomes in the GnomAD database, including 24,390 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 0.56 (24390 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66
• Publications: 11 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1906+14381G>C		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+14381G>C		intron_variant	Intron 3 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84369 AN: 151854 Hom.: 24361 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.556 AC: 84446 AN: 151972 Hom.: 24390 Cov.: 32 AF XY: 0.552 AC XY: 40969 AN XY: 74260

African (AFR) AF: 0.476 AC: 19731 AN: 41450

American (AMR) AF: 0.551 AC: 8408 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2206 AN: 3470

East Asian (EAS) AF: 0.199 AC: 1030 AN: 5164

South Asian (SAS) AF: 0.347 AC: 1670 AN: 4816

European-Finnish (FIN) AF: 0.639 AC: 6736 AN: 10548

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42803 AN: 67958

Other (OTH) AF: 0.554 AC: 1168 AN: 2110

Alfa AF: 0.595 Hom.: 3391

Bravo AF: 0.546

Asia WGS AF: 0.295 AC: 1027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.063
DANN	Benign	0.34
PhyloP100		-2.7
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: rs653752; hg19: chr11-100948110;