rs516693

Variant names:

• chr11-101093012-C-T
• rs516693
• NM_000926.4:c.1790-1136G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000926.4(PGR):​c.1790-1136G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,028 control chromosomes in the GnomAD database, including 2,439 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 0.17 (2439 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 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.1790-1136G>A		intron	N/A	NP_000917.3
	PGR	NM_001202474.3		c.1298-1136G>A		intron	N/A	NP_001189403.1
	PGR	NM_001271161.2		c.1298-1136G>A		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.1790-1136G>A		intron	N/A	ENSP00000325120.5
	PGR	ENST00000263463.9	TSL:1	c.1790-1136G>A		intron	N/A	ENSP00000263463.5
	PGR	ENST00000526300.5	TSL:1	n.1790-1136G>A		intron	N/A	ENSP00000436803.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25179 AN: 151910 Hom.: 2418 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.0637

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.166 AC: 25250 AN: 152028 Hom.: 2439 Cov.: 32 AF XY: 0.163 AC XY: 12144 AN XY: 74312

African (AFR) AF: 0.266 AC: 11031 AN: 41432

American (AMR) AF: 0.160 AC: 2435 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3472

East Asian (EAS) AF: 0.192 AC: 987 AN: 5152

South Asian (SAS) AF: 0.0648 AC: 312 AN: 4818

European-Finnish (FIN) AF: 0.102 AC: 1081 AN: 10578

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8373 AN: 67994

Other (OTH) AF: 0.156 AC: 330 AN: 2114

Alfa AF: 0.130 Hom.: 647

Bravo AF: 0.175

Asia WGS AF: 0.129 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.024
DANN	Benign	0.41
PhyloP100		-2.2
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: rs516693; hg19: chr11-100963743;