rs480851

Positions:

• chr11-101105460-A-G
• chr11-101105460-A-T

Variant summary

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

The NM_000926.4(PGR):​c.1790-13584T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 151,248 control chromosomes in the GnomAD database, including 5,646 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 0.24 (5646 hom., cov: 29)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.673

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGR	NM_000926.4	c.1790-13584T>C		intron_variant		ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.1790-13584T>C		intron_variant		1	NM_000926.4	ENSP00000325120	P1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 36951 AN: 151140 Hom.: 5648 Cov.: 29

Gnomad AFR AF: 0.0799

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.00579

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.244 AC: 36950 AN: 151248 Hom.: 5646 Cov.: 29 AF XY: 0.246 AC XY: 18133 AN XY: 73824

Gnomad4 AFR AF: 0.0799

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.00580

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.240

Alfa AF: 0.284 Hom.: 858

Bravo AF: 0.228

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.0
DANN	Benign	0.53

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: rs480851; hg19: chr11-100976191;