11-101065049-A-G

Variant names:

• chr11-101065049-A-G
• rs495997
• NM_000926.4:c.1907-2297T>C

Variant summary

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

The NM_000926.4(PGR):​c.1907-2297T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,010 control chromosomes in the GnomAD database, including 16,016 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 0.44 (16016 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824
• Publications: 6 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000926.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	NM_000926.4	MANE Select	c.1907-2297T>C		intron	N/A	NP_000917.3	P06401-1
	PGR	NM_001202474.3		c.1415-2297T>C		intron	N/A	NP_001189403.1	P06401-2
	PGR	NM_001271161.2		c.1415-13481T>C		intron	N/A	NP_001258090.1	P06401

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	ENST00000325455.10	TSL:1 MANE Select	c.1907-2297T>C		intron	N/A	ENSP00000325120.5	P06401-1
	PGR	ENST00000263463.9	TSL:1	c.1907-13481T>C		intron	N/A	ENSP00000263463.5	P06401-5
	PGR	ENST00000526300.5	TSL:1	n.1907-13481T>C		intron	N/A	ENSP00000436803.1	Q8NG45

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67540 AN: 151892 Hom.: 15981 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.445 AC: 67630 AN: 152010 Hom.: 16016 Cov.: 32 AF XY: 0.449 AC XY: 33329 AN XY: 74278

African (AFR) AF: 0.417 AC: 17297 AN: 41454

American (AMR) AF: 0.534 AC: 8155 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1910 AN: 3470

East Asian (EAS) AF: 0.983 AC: 5067 AN: 5154

South Asian (SAS) AF: 0.559 AC: 2697 AN: 4824

European-Finnish (FIN) AF: 0.397 AC: 4194 AN: 10554

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.395 AC: 26858 AN: 67978

Other (OTH) AF: 0.476 AC: 1003 AN: 2106

Alfa AF: 0.420 Hom.: 26841

Bravo AF: 0.455

Asia WGS AF: 0.776 AC: 2695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.44
PhyloP100		-0.82
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: rs495997; hg19: chr11-100935780;