rs10895068

chr11-101129483-C-T

Variant summary

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

The NM_000926.4(PGR):c.-413G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.037 in 238,568 control chromosomes in the GnomAD database, including 240 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 0.036 (142 hom., cov: 31)
  • Exomes 𝑓: 0.039 (98 hom.)
• Consequence: PGR NM_000926.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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-AS1 (HGNC:52650): (PGR antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGR	NM_000926.4	c.-413G>A		5_prime_UTR_variant	1/8	ENST00000325455.10
PGR-AS1	NR_073144.1	n.407C>T		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGR	ENST00000325455.10	c.-413G>A		5_prime_UTR_variant	1/8	1	NM_000926.4	P1
PGR-AS1	ENST00000632820.1	n.407C>T		non_coding_transcript_exon_variant	1/7	1
PGR	ENST00000534013.5	c.-201G>A		5_prime_UTR_variant	1/8	2
PGR	ENST00000619228.2	c.-413G>A		5_prime_UTR_variant	1/5	5

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5445 AN: 152078 Hom.: 142 Cov.: 31

Gnomad AFR AF: 0.00987

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.0375

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0569

Gnomad OTH AF: 0.0263

GnomAD4 exome AF: 0.0392 AC: 3389 AN: 86372 Hom.: 98 Cov.: 0 AF XY: 0.0383 AC XY: 1564 AN XY: 40830

Gnomad4 AFR exome AF: 0.0117

Gnomad4 AMR exome AF: 0.0238

Gnomad4 ASJ exome AF: 0.0352

Gnomad4 EAS exome AF: 0.000289

Gnomad4 SAS exome AF: 0.00514

Gnomad4 FIN exome AF: 0.0376

Gnomad4 NFE exome AF: 0.0510

Gnomad4 OTH exome AF: 0.0400

GnomAD4 genome AF: 0.0358 AC: 5445 AN: 152196 Hom.: 142 Cov.: 31 AF XY: 0.0331 AC XY: 2460 AN XY: 74420

Gnomad4 AFR AF: 0.00984

Gnomad4 AMR AF: 0.0321

Gnomad4 ASJ AF: 0.0363

Gnomad4 EAS AF: 0.000582

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.0375

Gnomad4 NFE AF: 0.0569

Gnomad4 OTH AF: 0.0261

Alfa AF: 0.0482 Hom.: 48

Bravo AF: 0.0335

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	8.3
Dann	Benign	0.91

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: rs10895068; hg19: chr11-101000214;