NM_000926.4:c.1790-4965A>G

Variant names:

• chr11-101096841-T-C
• rs572483
• NM_000926.4:c.1790-4965A>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.1790-4965A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,096 control chromosomes in the GnomAD database, including 6,833 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 0.30 (6833 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 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.1790-4965A>G		intron	N/A	NP_000917.3	P06401-1
	PGR	NM_001202474.3		c.1298-4965A>G		intron	N/A	NP_001189403.1	P06401-2
	PGR	NM_001271161.2		c.1298-4965A>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.1790-4965A>G		intron	N/A	ENSP00000325120.5	P06401-1
	PGR	ENST00000263463.9	TSL:1	c.1790-4965A>G		intron	N/A	ENSP00000263463.5	P06401-5
	PGR	ENST00000526300.5	TSL:1	n.1790-4965A>G		intron	N/A	ENSP00000436803.1	Q8NG45

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44895 AN: 151978 Hom.: 6813 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.296 AC: 44954 AN: 152096 Hom.: 6833 Cov.: 32 AF XY: 0.291 AC XY: 21660 AN XY: 74368

African (AFR) AF: 0.299 AC: 12398 AN: 41482

American (AMR) AF: 0.276 AC: 4221 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1157 AN: 3468

East Asian (EAS) AF: 0.193 AC: 996 AN: 5172

South Asian (SAS) AF: 0.258 AC: 1245 AN: 4822

European-Finnish (FIN) AF: 0.258 AC: 2731 AN: 10590

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21255 AN: 67978

Other (OTH) AF: 0.295 AC: 624 AN: 2112

Alfa AF: 0.309 Hom.: 2836

Bravo AF: 0.297

Asia WGS AF: 0.201 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.26
PhyloP100		-2.1
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: rs572483; hg19: chr11-100967572;