11-101105527-T-C

Variant names:

• chr11-101105527-T-C
• rs11224592
• NM_000926.4:c.1790-13651A>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.1790-13651A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 149,006 control chromosomes in the GnomAD database, including 7,865 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 0.32 (7865 hom., cov: 26)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	NM_000926.4	MANE Select	c.1790-13651A>G		intron	N/A	NP_000917.3	P06401-1
	PGR	NM_001202474.3		c.1298-13651A>G		intron	N/A	NP_001189403.1	P06401-2
	PGR	NM_001271161.2		c.1298-13651A>G		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.1790-13651A>G		intron	N/A	ENSP00000325120.5	P06401-1
	PGR	ENST00000263463.9	TSL:1	c.1790-13651A>G		intron	N/A	ENSP00000263463.5	P06401-5
	PGR	ENST00000526300.5	TSL:1	n.1790-13651A>G		intron	N/A	ENSP00000436803.1	Q8NG45

Frequencies

GnomAD3 genomes AF: 0.319 AC: 47486 AN: 148904 Hom.: 7841 Cov.: 26

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.319 AC: 47545 AN: 149006 Hom.: 7865 Cov.: 26 AF XY: 0.313 AC XY: 22726 AN XY: 72712

African (AFR) AF: 0.370 AC: 14805 AN: 39974

American (AMR) AF: 0.287 AC: 4308 AN: 14988

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1182 AN: 3450

East Asian (EAS) AF: 0.193 AC: 987 AN: 5110

South Asian (SAS) AF: 0.259 AC: 1229 AN: 4754

European-Finnish (FIN) AF: 0.248 AC: 2470 AN: 9972

Middle Eastern (MID) AF: 0.297 AC: 86 AN: 290

European-Non Finnish (NFE) AF: 0.320 AC: 21603 AN: 67502

Other (OTH) AF: 0.309 AC: 635 AN: 2056

Alfa AF: 0.318 Hom.: 1025

Bravo AF: 0.325

Asia WGS AF: 0.204 AC: 711 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	2.1
DANN	Benign	0.54
PhyloP100		-1.0
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: rs11224592; hg19: chr11-100976258;