rs508653

Positions:

• chr11-101091469-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000926.4(PGR):​c.1906+291G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,144 control chromosomes in the GnomAD database, including 2,450 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 0.17 (2450 hom., cov: 33)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGR	NM_000926.4	c.1906+291G>T		intron_variant		ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.1906+291G>T		intron_variant		1	NM_000926.4	ENSP00000325120	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25213 AN: 152026 Hom.: 2429 Cov.: 33

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.0637

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.166 AC: 25284 AN: 152144 Hom.: 2450 Cov.: 33 AF XY: 0.164 AC XY: 12175 AN XY: 74384

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.0648

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.156

Alfa AF: 0.129 Hom.: 626

Bravo AF: 0.176

Asia WGS AF: 0.129 AC: 448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.5
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs508653; hg19: chr11-100962200;