rs526487

Variant names:

• chr11-101049844-A-G
• rs526487
• NM_000926.4:c.2488+85T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-101049844-A-G
• chr11-101049844-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000926.4(PGR):​c.2488+85T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 930,456 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.2488+85T>C		intron	N/A	NP_000917.3	P06401-1
	PGR	NM_001202474.3		c.1996+85T>C		intron	N/A	NP_001189403.1	P06401-2
	PGR	NM_001271161.2		c.1690+85T>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.2488+85T>C		intron	N/A	ENSP00000325120.5	P06401-1
	PGR	ENST00000263463.9	TSL:1	c.2182+85T>C		intron	N/A	ENSP00000263463.5	P06401-5
	PGR	ENST00000526300.5	TSL:1	n.2051+1580T>C		intron	N/A	ENSP00000436803.1	Q8NG45

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000215 AC: 2 AN: 930456 Hom.: 0 AF XY: 0.00000206 AC XY: 1 AN XY: 484730

African (AFR) AF: 0.00 AC: 0 AN: 22892

American (AMR) AF: 0.00 AC: 0 AN: 41944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22164

East Asian (EAS) AF: 0.00 AC: 0 AN: 36042

South Asian (SAS) AF: 0.0000136 AC: 1 AN: 73556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4126

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 642394

Other (OTH) AF: 0.0000237 AC: 1 AN: 42142

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 257

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.67
PhyloP100		0.56

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: rs526487; hg19: chr11-100920575;