chr11-101046524-T-C

Variant names:

• chr11-101046524-T-C
• rs572402
• NM_000926.4:c.2488+3405A>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.2488+3405A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,338 control chromosomes in the GnomAD database, including 6,149 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 (6149 hom., cov: 29)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.2488+3405A>G		intron_variant	Intron 6 of 7	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.2488+3405A>G		intron_variant	Intron 6 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42074 AN: 151220 Hom.: 6127 Cov.: 29

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.279 AC: 42158 AN: 151338 Hom.: 6149 Cov.: 29 AF XY: 0.273 AC XY: 20198 AN XY: 73952

African (AFR) AF: 0.376 AC: 15452 AN: 41148

American (AMR) AF: 0.283 AC: 4298 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1340 AN: 3460

East Asian (EAS) AF: 0.221 AC: 1137 AN: 5138

South Asian (SAS) AF: 0.127 AC: 610 AN: 4804

European-Finnish (FIN) AF: 0.217 AC: 2258 AN: 10420

Middle Eastern (MID) AF: 0.269 AC: 78 AN: 290

European-Non Finnish (NFE) AF: 0.238 AC: 16143 AN: 67880

Other (OTH) AF: 0.289 AC: 606 AN: 2098

Alfa AF: 0.262 Hom.: 702

Bravo AF: 0.291

Asia WGS AF: 0.192 AC: 669 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.2
DANN	Benign	0.82
PhyloP100		-0.086
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: rs572402; hg19: chr11-100917255;