chr11-101034566-G-A

Variant names:

• chr11-101034566-G-A
• rs471767
• NM_000926.4:c.*4550C>T

Variant summary

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

The NM_000926.4(PGR):​c.*4550C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 174,920 control chromosomes in the GnomAD database, including 45,702 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 0.72 (39241 hom., cov: 34)
  • Exomes 𝑓: 0.75 (6461 hom.)
• Consequence: PGR NM_000926.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349
• Publications: 29 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000926.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	NM_000926.4	MANE Select	c.*4550C>T		3_prime_UTR	Exon 8 of 8	NP_000917.3
	PGR	NM_001202474.3		c.*4550C>T		3_prime_UTR	Exon 8 of 8	NP_001189403.1
	PGR	NM_001271161.2		c.*4550C>T		3_prime_UTR	Exon 7 of 7	NP_001258090.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	ENST00000325455.10	TSL:1 MANE Select	c.*4550C>T		3_prime_UTR	Exon 8 of 8	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108781 AN: 152008 Hom.: 39183 Cov.: 34

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.713

GnomAD4 exome AF: 0.745 AC: 16990 AN: 22794 Hom.: 6461 Cov.: 0 AF XY: 0.746 AC XY: 7801 AN XY: 10460

African (AFR) AF: 0.725 AC: 515 AN: 710

American (AMR) AF: 0.774 AC: 384 AN: 496

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 1089 AN: 1532

East Asian (EAS) AF: 0.956 AC: 4518 AN: 4726

South Asian (SAS) AF: 0.718 AC: 145 AN: 202

European-Finnish (FIN) AF: 0.667 AC: 8 AN: 12

Middle Eastern (MID) AF: 0.717 AC: 109 AN: 152

European-Non Finnish (NFE) AF: 0.679 AC: 8938 AN: 13156

Other (OTH) AF: 0.710 AC: 1284 AN: 1808

GnomAD4 genome AF: 0.716 AC: 108896 AN: 152126 Hom.: 39241 Cov.: 34 AF XY: 0.719 AC XY: 53445 AN XY: 74350

African (AFR) AF: 0.720 AC: 29894 AN: 41504

American (AMR) AF: 0.761 AC: 11633 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2477 AN: 3468

East Asian (EAS) AF: 0.946 AC: 4900 AN: 5180

South Asian (SAS) AF: 0.717 AC: 3464 AN: 4830

European-Finnish (FIN) AF: 0.721 AC: 7616 AN: 10558

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.687 AC: 46694 AN: 67988

Other (OTH) AF: 0.714 AC: 1509 AN: 2114

Alfa AF: 0.698 Hom.: 109795

Bravo AF: 0.720

Asia WGS AF: 0.833 AC: 2893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.43
PhyloP100		-0.35
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: rs471767; hg19: chr11-100905297;