11-101118717-T-C

Variant names:

• chr11-101118717-T-C
• rs493957
• NM_000926.4:c.1789+7290A>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.1789+7290A>G 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 152,126 control chromosomes in the GnomAD database, including 5,801 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 (5801 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• 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=-0.91).
• 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+7290A>G		intron	N/A	NP_000917.3
	PGR	NM_001202474.3		c.1297+7290A>G		intron	N/A	NP_001189403.1
	PGR	NM_001271161.2		c.1297+7290A>G		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+7290A>G		intron	N/A	ENSP00000325120.5
	PGR	ENST00000263463.9	TSL:1	c.1789+7290A>G		intron	N/A	ENSP00000263463.5
	PGR	ENST00000526300.5	TSL:1	n.1789+7290A>G		intron	N/A	ENSP00000436803.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38338 AN: 152008 Hom.: 5804 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.252 AC: 38339 AN: 152126 Hom.: 5801 Cov.: 32 AF XY: 0.253 AC XY: 18837 AN XY: 74364

African (AFR) AF: 0.105 AC: 4366 AN: 41532

American (AMR) AF: 0.249 AC: 3803 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 767 AN: 3466

East Asian (EAS) AF: 0.00579 AC: 30 AN: 5182

South Asian (SAS) AF: 0.202 AC: 977 AN: 4826

European-Finnish (FIN) AF: 0.378 AC: 3987 AN: 10546

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

European-Non Finnish (NFE) AF: 0.346 AC: 23543 AN: 67976

Other (OTH) AF: 0.248 AC: 524 AN: 2112

Alfa AF: 0.281 Hom.: 875

Bravo AF: 0.236

Asia WGS AF: 0.106 AC: 368 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.81
PhyloP100		-0.32
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: rs493957; hg19: chr11-100989448;