rs471767

Positions:

• chr11-101034566-G-A
• chr11-101034566-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.*4550C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 174,920 control chromosomes in the GnomAD database, including 45,702 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 0.72 (39241 hom., cov: 34)
  • Exomes 𝑓: 0.75 (6461 hom.)
• Consequence: PGR NM_000926.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349

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 (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGR	NM_000926.4	c.*4550C>T		3_prime_UTR_variant	8/8	ENST00000325455.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGR	ENST00000325455.10	c.*4550C>T		3_prime_UTR_variant	8/8	1	NM_000926.4	P1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108781 AN: 152008 Hom.: 39183 Cov.: 34

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.713

GnomAD4 exome AF: 0.745 AC: 16990 AN: 22794 Hom.: 6461 Cov.: 0 AF XY: 0.746 AC XY: 7801 AN XY: 10460

Gnomad4 AFR exome AF: 0.725

Gnomad4 AMR exome AF: 0.774

Gnomad4 ASJ exome AF: 0.711

Gnomad4 EAS exome AF: 0.956

Gnomad4 SAS exome AF: 0.718

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.679

Gnomad4 OTH exome AF: 0.710

GnomAD4 genome AF: 0.716 AC: 108896 AN: 152126 Hom.: 39241 Cov.: 34 AF XY: 0.719 AC XY: 53445 AN XY: 74350

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.687

Gnomad4 OTH AF: 0.714

Alfa AF: 0.689 Hom.: 45434

Bravo AF: 0.720

Asia WGS AF: 0.833 AC: 2893 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	0.20
DANN	Benign	0.43

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: rs471767; hg19: chr11-100905297;