rs1870019

Variant names:

• chr11-101030742-A-G
• rs1870019
• NM_000926.4:c.*8374T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000926.4(PGR):​c.*8374T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 205,830 control chromosomes in the GnomAD database, including 6,382 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 0.22 (4658 hom., cov: 32)
  • Exomes 𝑓: 0.23 (1724 hom.)
• Consequence: PGR NM_000926.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• Publications: 1 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 (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.*8374T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.*8374T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33851 AN: 152026 Hom.: 4660 Cov.: 32

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.229 AC: 12308 AN: 53686 Hom.: 1724 Cov.: 0 AF XY: 0.234 AC XY: 5836 AN XY: 24906

African (AFR) AF: 0.0711 AC: 169 AN: 2376

American (AMR) AF: 0.234 AC: 357 AN: 1528

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 845 AN: 3512

East Asian (EAS) AF: 0.000240 AC: 2 AN: 8326

South Asian (SAS) AF: 0.177 AC: 83 AN: 468

European-Finnish (FIN) AF: 0.250 AC: 9 AN: 36

Middle Eastern (MID) AF: 0.339 AC: 112 AN: 330

European-Non Finnish (NFE) AF: 0.296 AC: 9650 AN: 32572

Other (OTH) AF: 0.238 AC: 1081 AN: 4538

GnomAD4 genome AF: 0.222 AC: 33851 AN: 152144 Hom.: 4658 Cov.: 32 AF XY: 0.223 AC XY: 16584 AN XY: 74362

African (AFR) AF: 0.0723 AC: 3003 AN: 41526

American (AMR) AF: 0.225 AC: 3445 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3470

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5180

South Asian (SAS) AF: 0.196 AC: 944 AN: 4820

European-Finnish (FIN) AF: 0.346 AC: 3656 AN: 10558

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.312 AC: 21227 AN: 67992

Other (OTH) AF: 0.230 AC: 485 AN: 2110

Alfa AF: 0.276 Hom.: 2139

Bravo AF: 0.206

Asia WGS AF: 0.104 AC: 361 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	1.5
DANN	Benign	0.55
PhyloP100		-0.019
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: rs1870019; hg19: chr11-100901473; COSMIC: COSV57672248;