11-101096821-A-G

Position:

• chr11-101096821-A-G

Variant summary

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

The NM_000926.4(PGR):​c.1790-4945T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 152,176 control chromosomes in the GnomAD database, including 58,128 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 0.87 (58128 hom., cov: 33)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299

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]

PGR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGR	NM_000926.4	c.1790-4945T>C		intron_variant		ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.1790-4945T>C		intron_variant		1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132124 AN: 152058 Hom.: 58086 Cov.: 33

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.880

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

GnomAD4 genome AF: 0.869 AC: 132219 AN: 152176 Hom.: 58128 Cov.: 33 AF XY: 0.872 AC XY: 64857 AN XY: 74404

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.904

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.951

Gnomad4 FIN AF: 0.925

Gnomad4 NFE AF: 0.925

Gnomad4 OTH AF: 0.881

Alfa AF: 0.893 Hom.: 7684

Bravo AF: 0.861

Asia WGS AF: 0.958 AC: 3332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.0
DANN	Benign	0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs601040; hg19: chr11-100967552;