rs561650

Positions:

• chr11-101045163-T-C
• chr11-101045163-T-G

Variant summary

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

The NM_000926.4(PGR):​c.2489-3061A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 152,194 control chromosomes in the GnomAD database, including 463 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 0.075 (463 hom., cov: 31)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGR	NM_000926.4	c.2489-3061A>G		intron_variant		ENST00000325455.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGR	ENST00000325455.10	c.2489-3061A>G		intron_variant		1	NM_000926.4	P1

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11357 AN: 152076 Hom.: 464 Cov.: 31

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.0658

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.0888

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

GnomAD4 genome AF: 0.0747 AC: 11366 AN: 152194 Hom.: 463 Cov.: 31 AF XY: 0.0753 AC XY: 5605 AN XY: 74402

Gnomad4 AFR AF: 0.0623

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.0328

Gnomad4 FIN AF: 0.0658

Gnomad4 NFE AF: 0.0701

Gnomad4 OTH AF: 0.0883

Alfa AF: 0.0713 Hom.: 54

Bravo AF: 0.0795

Asia WGS AF: 0.0800 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.3
DANN	Benign	0.75

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: rs561650; hg19: chr11-100915894;