11-101076990-A-T

Variant names:

• chr11-101076990-A-T
• rs1145463
• NM_000926.4:c.1907-14238T>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.1907-14238T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.31 (5218 hom., cov: 20)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1907-14238T>A		intron_variant	Intron 3 of 7	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.1907-14238T>A		intron_variant	Intron 3 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.308 AC: 34667 AN: 112608 Hom.: 5220 Cov.: 20

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.00667

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.308 AC: 34666 AN: 112666 Hom.: 5218 Cov.: 20 AF XY: 0.311 AC XY: 16711 AN XY: 53666

African (AFR) AF: 0.125 AC: 3161 AN: 25260

American (AMR) AF: 0.320 AC: 3350 AN: 10464

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 746 AN: 2862

East Asian (EAS) AF: 0.00668 AC: 27 AN: 4042

South Asian (SAS) AF: 0.227 AC: 890 AN: 3914

European-Finnish (FIN) AF: 0.459 AC: 2907 AN: 6328

Middle Eastern (MID) AF: 0.440 AC: 81 AN: 184

European-Non Finnish (NFE) AF: 0.397 AC: 22791 AN: 57394

Other (OTH) AF: 0.313 AC: 473 AN: 1512

Alfa AF: 0.275 Hom.: 733

Bravo AF: 0.229

Asia WGS AF: 0.103 AC: 357 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.85
PhyloP100		-0.41
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: rs1145463; hg19: chr11-100947721;