11-101063583-G-C

Position:

• chr11-101063583-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.1907-831C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,128 control chromosomes in the GnomAD database, including 42,717 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 0.75 (42713 hom., cov: 32)
  • Exomes 𝑓: 0.58 (4 hom.)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGR	NM_000926.4	c.1907-831C>G		intron_variant		ENST00000325455.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGR	ENST00000325455.10	c.1907-831C>G		intron_variant		1	NM_000926.4	P1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113572 AN: 151984 Hom.: 42658 Cov.: 32

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.750

GnomAD4 exome AF: 0.577 AC: 15 AN: 26 Hom.: 4 Cov.: 0 AF XY: 0.591 AC XY: 13 AN XY: 22

Gnomad4 AFR exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.545

GnomAD4 genome AF: 0.747 AC: 113683 AN: 152102 Hom.: 42713 Cov.: 32 AF XY: 0.751 AC XY: 55837 AN XY: 74338

Gnomad4 AFR AF: 0.717

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.769

Gnomad4 EAS AF: 0.989

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.731

Gnomad4 OTH AF: 0.752

Alfa AF: 0.743 Hom.: 5198

Bravo AF: 0.747

Asia WGS AF: 0.894 AC: 3107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.65

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: rs660149; hg19: chr11-100934314;