rs547378

chr11-101052208-G-Achr11-101052208-G-T

Variant summary

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

The NM_000926.4(PGR):c.2213-640C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,222 control chromosomes in the GnomAD database, including 5,531 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 0.27 (5531 hom., cov: 30)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGR	NM_000926.4	c.2213-640C>T		intron_variant		ENST00000325455.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGR	ENST00000325455.10	c.2213-640C>T		intron_variant		1	NM_000926.4	P1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40244 AN: 151104 Hom.: 5518 Cov.: 30

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.267 AC: 40315 AN: 151222 Hom.: 5531 Cov.: 30 AF XY: 0.262 AC XY: 19305 AN XY: 73818

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.281

Alfa AF: 0.235 Hom.: 2010

Bravo AF: 0.277

Asia WGS AF: 0.190 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	4.0
Dann	Benign	0.59

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: rs547378; hg19: chr11-100922939; COSMIC: COSV54811768; COSMIC: COSV54811768;