rs613120

Variant names:

• chr11-101103547-A-G
• rs613120
• NM_000926.4:c.1790-11671T>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.1790-11671T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,886 control chromosomes in the GnomAD database, including 16,938 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 0.47 (16938 hom., cov: 31)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 10 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 (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1790-11671T>C		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.1790-11671T>C		intron_variant	Intron 2 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71036 AN: 151768 Hom.: 16912 Cov.: 31

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.468 AC: 71106 AN: 151886 Hom.: 16938 Cov.: 31 AF XY: 0.460 AC XY: 34108 AN XY: 74206

African (AFR) AF: 0.501 AC: 20740 AN: 41418

American (AMR) AF: 0.437 AC: 6669 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2063 AN: 3466

East Asian (EAS) AF: 0.204 AC: 1049 AN: 5138

South Asian (SAS) AF: 0.337 AC: 1622 AN: 4812

European-Finnish (FIN) AF: 0.417 AC: 4406 AN: 10556

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32963 AN: 67922

Other (OTH) AF: 0.470 AC: 990 AN: 2108

Alfa AF: 0.484 Hom.: 3505

Bravo AF: 0.472

Asia WGS AF: 0.268 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.62
DANN	Benign	0.41
PhyloP100		-1.3
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: rs613120; hg19: chr11-100974278;