11-101108744-T-C

Variant names:

• chr11-101108744-T-C
• rs11224598
• NM_000926.4:c.1790-16868A>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.1790-16868A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,036 control chromosomes in the GnomAD database, including 8,072 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 (8072 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1790-16868A>G		intron_variant	Intron 2 of 7	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.1790-16868A>G		intron_variant	Intron 2 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48724 AN: 151918 Hom.: 8046 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.321 AC: 48791 AN: 152036 Hom.: 8072 Cov.: 32 AF XY: 0.315 AC XY: 23431 AN XY: 74318

African (AFR) AF: 0.371 AC: 15365 AN: 41462

American (AMR) AF: 0.289 AC: 4409 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3466

East Asian (EAS) AF: 0.194 AC: 1002 AN: 5176

South Asian (SAS) AF: 0.265 AC: 1276 AN: 4824

European-Finnish (FIN) AF: 0.260 AC: 2741 AN: 10560

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21816 AN: 67954

Other (OTH) AF: 0.312 AC: 659 AN: 2112

Alfa AF: 0.303 Hom.: 4095

Bravo AF: 0.326

Asia WGS AF: 0.206 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.66
PhyloP100		-0.20
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: rs11224598; hg19: chr11-100979475;