11-101094508-G-T

Variant names:

• chr11-101094508-G-T
• rs508533
• NM_000926.4:c.1790-2632C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000926.4(PGR):​c.1790-2632C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 151,834 control chromosomes in the GnomAD database, including 26,593 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 0.58 (26593 hom., cov: 31)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1790-2632C>A		intron_variant	Intron 2 of 7	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.1790-2632C>A		intron_variant	Intron 2 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88566 AN: 151714 Hom.: 26562 Cov.: 31

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.584 AC: 88647 AN: 151834 Hom.: 26593 Cov.: 31 AF XY: 0.578 AC XY: 42920 AN XY: 74198

African (AFR) AF: 0.557 AC: 23025 AN: 41362

American (AMR) AF: 0.564 AC: 8615 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2240 AN: 3466

East Asian (EAS) AF: 0.209 AC: 1077 AN: 5156

South Asian (SAS) AF: 0.348 AC: 1672 AN: 4802

European-Finnish (FIN) AF: 0.641 AC: 6748 AN: 10520

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43319 AN: 67950

Other (OTH) AF: 0.570 AC: 1206 AN: 2114

Alfa AF: 0.507 Hom.: 1477

Bravo AF: 0.578

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.92
DANN	Benign	0.36
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs508533; hg19: chr11-100965239;