rs491893

Positions:

• chr11-101098416-G-A
• chr11-101098416-G-C

Variant summary

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

The NM_000926.4(PGR):​c.1790-6540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 151,974 control chromosomes in the GnomAD database, including 40,375 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 0.71 (40375 hom., cov: 31)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGR	NM_000926.4	c.1790-6540C>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.1790-6540C>T		intron_variant		1	NM_000926.4	ENSP00000325120	P1

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108405 AN: 151858 Hom.: 40350 Cov.: 31

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.740

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.714 AC: 108473 AN: 151974 Hom.: 40375 Cov.: 31 AF XY: 0.707 AC XY: 52480 AN XY: 74264

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.816

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.711

Alfa AF: 0.769 Hom.: 5662

Bravo AF: 0.700

Asia WGS AF: 0.374 AC: 1306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.3
DANN	Benign	0.46

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: rs491893; hg19: chr11-100969147;