rs481775

Variant names:

• chr11-101123944-G-A
• rs481775
• NM_000926.4:c.1789+2063C>T

Variant summary

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

The NM_000926.4(PGR):​c.1789+2063C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,124 control chromosomes in the GnomAD database, including 5,650 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 0.24 (5650 hom., cov: 33)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1789+2063C>T		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.1789+2063C>T		intron_variant	Intron 2 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37135 AN: 152006 Hom.: 5653 Cov.: 33

Gnomad AFR AF: 0.0803

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.244 AC: 37133 AN: 152124 Hom.: 5650 Cov.: 33 AF XY: 0.246 AC XY: 18273 AN XY: 74350

African (AFR) AF: 0.0802 AC: 3332 AN: 41528

American (AMR) AF: 0.246 AC: 3764 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 764 AN: 3466

East Asian (EAS) AF: 0.00579 AC: 30 AN: 5182

South Asian (SAS) AF: 0.197 AC: 949 AN: 4822

European-Finnish (FIN) AF: 0.378 AC: 3995 AN: 10564

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23443 AN: 67958

Other (OTH) AF: 0.243 AC: 514 AN: 2112

Alfa AF: 0.262 Hom.: 943

Bravo AF: 0.227

Asia WGS AF: 0.104 AC: 363 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.21
PhyloP100		-0.047
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: rs481775; hg19: chr11-100994675;