chr11-101124135-T-C

Variant names:

• chr11-101124135-T-C
• rs582691
• NM_000926.4:c.1789+1872A>G

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+1872A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 152,192 control chromosomes in the GnomAD database, including 57,950 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 (57950 hom., cov: 33)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 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.1789+1872A>G		intron	N/A	NP_000917.3	P06401-1
	PGR	NM_001202474.3		c.1297+1872A>G		intron	N/A	NP_001189403.1	P06401-2
	PGR	NM_001271161.2		c.1297+1872A>G		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.1789+1872A>G		intron	N/A	ENSP00000325120.5	P06401-1
	PGR	ENST00000263463.9	TSL:1	c.1789+1872A>G		intron	N/A	ENSP00000263463.5	P06401-5
	PGR	ENST00000526300.5	TSL:1	n.1789+1872A>G		intron	N/A	ENSP00000436803.1	Q8NG45

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131866 AN: 152074 Hom.: 57908 Cov.: 33

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.892

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: 0.867 AC: 131964 AN: 152192 Hom.: 57950 Cov.: 33 AF XY: 0.870 AC XY: 64738 AN XY: 74410

African (AFR) AF: 0.713 AC: 29578 AN: 41486

American (AMR) AF: 0.903 AC: 13809 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3256 AN: 3472

East Asian (EAS) AF: 0.990 AC: 5127 AN: 5178

South Asian (SAS) AF: 0.951 AC: 4591 AN: 4826

European-Finnish (FIN) AF: 0.925 AC: 9820 AN: 10618

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.925 AC: 62890 AN: 68000

Other (OTH) AF: 0.880 AC: 1863 AN: 2116

Alfa AF: 0.897 Hom.: 35201

Bravo AF: 0.859

Asia WGS AF: 0.958 AC: 3330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.47
PhyloP100		-0.32
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: rs582691; hg19: chr11-100994866;