rs485283

Variant names:

• chr11-101119716-A-G
• rs485283
• NM_000926.4:c.1789+6291T>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.1789+6291T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,162 control chromosomes in the GnomAD database, including 5,799 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 0.25 (5799 hom., cov: 33)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	NM_000926.4	MANE Select	c.1789+6291T>C		intron	N/A	NP_000917.3
	PGR	NM_001202474.3		c.1297+6291T>C		intron	N/A	NP_001189403.1
	PGR	NM_001271161.2		c.1297+6291T>C		intron	N/A	NP_001258090.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	ENST00000325455.10	TSL:1 MANE Select	c.1789+6291T>C		intron	N/A	ENSP00000325120.5
	PGR	ENST00000263463.9	TSL:1	c.1789+6291T>C		intron	N/A	ENSP00000263463.5
	PGR	ENST00000526300.5	TSL:1	n.1789+6291T>C		intron	N/A	ENSP00000436803.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38338 AN: 152044 Hom.: 5802 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.252 AC: 38339 AN: 152162 Hom.: 5799 Cov.: 33 AF XY: 0.253 AC XY: 18848 AN XY: 74412

African (AFR) AF: 0.105 AC: 4374 AN: 41552

American (AMR) AF: 0.249 AC: 3804 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 769 AN: 3468

East Asian (EAS) AF: 0.00579 AC: 30 AN: 5178

South Asian (SAS) AF: 0.203 AC: 978 AN: 4824

European-Finnish (FIN) AF: 0.377 AC: 3985 AN: 10562

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23535 AN: 67970

Other (OTH) AF: 0.247 AC: 523 AN: 2114

Alfa AF: 0.297 Hom.: 1767

Bravo AF: 0.236

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.42
PhyloP100		0.18
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: rs485283; hg19: chr11-100990447;