rs518382

Variant names:

• chr11-101060386-C-T
• rs518382
• NM_000926.4:c.2212+2061G>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.2212+2061G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,042 control chromosomes in the GnomAD database, including 6,418 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 (6418 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.2212+2061G>A		intron_variant	Intron 4 of 7	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.2212+2061G>A		intron_variant	Intron 4 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42953 AN: 151924 Hom.: 6404 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.283 AC: 43027 AN: 152042 Hom.: 6418 Cov.: 32 AF XY: 0.278 AC XY: 20657 AN XY: 74302

African (AFR) AF: 0.386 AC: 16017 AN: 41452

American (AMR) AF: 0.286 AC: 4363 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3472

East Asian (EAS) AF: 0.222 AC: 1152 AN: 5178

South Asian (SAS) AF: 0.130 AC: 625 AN: 4824

European-Finnish (FIN) AF: 0.224 AC: 2366 AN: 10564

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

European-Non Finnish (NFE) AF: 0.238 AC: 16196 AN: 67956

Other (OTH) AF: 0.295 AC: 623 AN: 2114

Alfa AF: 0.248 Hom.: 2883

Bravo AF: 0.295

Asia WGS AF: 0.197 AC: 684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.32
DANN	Benign	0.56
PhyloP100		-0.72
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: rs518382; hg19: chr11-100931117;