11-101034325-C-T

Variant names:

• chr11-101034325-C-T
• rs11224561
• NM_000926.4:c.*4791G>A

Variant summary

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

The NM_000926.4(PGR):​c.*4791G>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 0.174 in 217,570 control chromosomes in the GnomAD database, including 5,987 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 0.16 (3061 hom., cov: 33)
  • Exomes 𝑓: 0.21 (2926 hom.)
• Consequence: PGR NM_000926.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.*4791G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455	c.*4791G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23946 AN: 152152 Hom.: 3047 Cov.: 33

Gnomad AFR AF: 0.0789

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.213 AC: 13906 AN: 65300 Hom.: 2926 Cov.: 0 AF XY: 0.208 AC XY: 6273 AN XY: 30220

Gnomad4 AFR exome AF: 0.0837

Gnomad4 AMR exome AF: 0.289

Gnomad4 ASJ exome AF: 0.0991

Gnomad4 EAS exome AF: 0.700

Gnomad4 SAS exome AF: 0.358

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.158 AC: 23984 AN: 152270 Hom.: 3061 Cov.: 33 AF XY: 0.168 AC XY: 12520 AN XY: 74448

Gnomad4 AFR AF: 0.0789

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.143

Alfa AF: 0.0808 Hom.: 157

Bravo AF: 0.158

Asia WGS AF: 0.514 AC: 1782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.99
DANN	Benign	0.62

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: rs11224561; hg19: chr11-100905056;