rs501732

Variant names:

• chr11-101122341-G-A
• rs501732
• NM_000926.4:c.1789+3666C>T

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+3666C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 152,070 control chromosomes in the GnomAD database, including 39,396 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 0.70 (39396 hom., cov: 31)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.869
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.821 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+3666C>T		intron	N/A	NP_000917.3
	PGR	NM_001202474.3		c.1297+3666C>T		intron	N/A	NP_001189403.1
	PGR	NM_001271161.2		c.1297+3666C>T		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+3666C>T		intron	N/A	ENSP00000325120.5
	PGR	ENST00000263463.9	TSL:1	c.1789+3666C>T		intron	N/A	ENSP00000263463.5
	PGR	ENST00000526300.5	TSL:1	n.1789+3666C>T		intron	N/A	ENSP00000436803.1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106856 AN: 151952 Hom.: 39371 Cov.: 31

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.703 AC: 106923 AN: 152070 Hom.: 39396 Cov.: 31 AF XY: 0.696 AC XY: 51722 AN XY: 74336

African (AFR) AF: 0.553 AC: 22908 AN: 41444

American (AMR) AF: 0.678 AC: 10360 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2828 AN: 3468

East Asian (EAS) AF: 0.230 AC: 1188 AN: 5162

South Asian (SAS) AF: 0.536 AC: 2581 AN: 4818

European-Finnish (FIN) AF: 0.796 AC: 8422 AN: 10578

Middle Eastern (MID) AF: 0.733 AC: 214 AN: 292

European-Non Finnish (NFE) AF: 0.826 AC: 56207 AN: 68010

Other (OTH) AF: 0.704 AC: 1487 AN: 2112

Alfa AF: 0.783 Hom.: 22887

Bravo AF: 0.688

Asia WGS AF: 0.375 AC: 1309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.38
PhyloP100		0.87
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: rs501732; hg19: chr11-100993072;