rs608995

Positions:

• chr11-101035002-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.*4114T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 197,360 control chromosomes in the GnomAD database, including 7,146 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 (5664 hom., cov: 32)
  • Exomes 𝑓: 0.26 (1482 hom.)
• Consequence: PGR NM_000926.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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]

PGR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGR	NM_000926.4	c.*4114T>A		3_prime_UTR_variant	8/8	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455	c.*4114T>A		3_prime_UTR_variant	8/8	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40705 AN: 151982 Hom.: 5645 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.284

GnomAD4 exome AF: 0.255 AC: 11548 AN: 45260 Hom.: 1482 Cov.: 0 AF XY: 0.254 AC XY: 5319 AN XY: 20932

Gnomad4 AFR exome AF: 0.322

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.370

Gnomad4 EAS exome AF: 0.234

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.0625

Gnomad4 NFE exome AF: 0.243

Gnomad4 OTH exome AF: 0.269

GnomAD4 genome AF: 0.268 AC: 40782 AN: 152100 Hom.: 5664 Cov.: 32 AF XY: 0.263 AC XY: 19561 AN XY: 74360

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.286

Alfa AF: 0.257 Hom.: 696

Bravo AF: 0.279

Asia WGS AF: 0.196 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.24
DANN	Benign	0.49

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: rs608995; hg19: chr11-100905733;