11-101043916-C-T

Variant names:

• chr11-101043916-C-T
• rs523630
• NM_000926.4:c.2489-1814G>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.2489-1814G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,016 control chromosomes in the GnomAD database, including 6,019 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 0.28 (6019 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.2489-1814G>A		intron_variant	Intron 6 of 7	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.2489-1814G>A		intron_variant	Intron 6 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41786 AN: 151898 Hom.: 6000 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.275 AC: 41868 AN: 152016 Hom.: 6019 Cov.: 32 AF XY: 0.270 AC XY: 20082 AN XY: 74310

African (AFR) AF: 0.364 AC: 15103 AN: 41448

American (AMR) AF: 0.282 AC: 4307 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1336 AN: 3462

East Asian (EAS) AF: 0.223 AC: 1150 AN: 5154

South Asian (SAS) AF: 0.127 AC: 613 AN: 4824

European-Finnish (FIN) AF: 0.217 AC: 2288 AN: 10568

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16151 AN: 67958

Other (OTH) AF: 0.287 AC: 607 AN: 2114

Alfa AF: 0.147 Hom.: 257

Bravo AF: 0.287

Asia WGS AF: 0.192 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.62
PhyloP100		-0.37
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: rs523630; hg19: chr11-100914647;