11-101040264-T-C

Variant names:

• chr11-101040264-T-C
• rs563656
• NM_000926.4:c.2647-993A>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.2647-993A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,920 control chromosomes in the GnomAD database, including 6,039 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 0.28 (6039 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.908
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.2647-993A>G		intron_variant	Intron 7 of 7	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.2647-993A>G		intron_variant	Intron 7 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41819 AN: 151804 Hom.: 6019 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.276 AC: 41900 AN: 151920 Hom.: 6039 Cov.: 32 AF XY: 0.270 AC XY: 20053 AN XY: 74288

African (AFR) AF: 0.365 AC: 15122 AN: 41416

American (AMR) AF: 0.281 AC: 4293 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1340 AN: 3466

East Asian (EAS) AF: 0.225 AC: 1160 AN: 5164

South Asian (SAS) AF: 0.129 AC: 622 AN: 4828

European-Finnish (FIN) AF: 0.217 AC: 2299 AN: 10592

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16140 AN: 67884

Other (OTH) AF: 0.290 AC: 611 AN: 2110

Alfa AF: 0.245 Hom.: 2541

Bravo AF: 0.287

Asia WGS AF: 0.192 AC: 669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.78
PhyloP100		-0.91
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: rs563656; hg19: chr11-100910995;