rs537681

Variant names:

• chr11-101117303-C-T
• rs537681
• NM_000926.4:c.1789+8704G>A

Variant summary

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

The NM_000926.4(PGR):​c.1789+8704G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 151,980 control chromosomes in the GnomAD database, including 39,348 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 0.70 (39348 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1789+8704G>A		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.1789+8704G>A		intron_variant	Intron 2 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106707 AN: 151862 Hom.: 39323 Cov.: 32

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.703 AC: 106774 AN: 151980 Hom.: 39348 Cov.: 32 AF XY: 0.695 AC XY: 51643 AN XY: 74286

African (AFR) AF: 0.553 AC: 22901 AN: 41412

American (AMR) AF: 0.678 AC: 10359 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2829 AN: 3470

East Asian (EAS) AF: 0.214 AC: 1109 AN: 5174

South Asian (SAS) AF: 0.535 AC: 2578 AN: 4820

European-Finnish (FIN) AF: 0.797 AC: 8400 AN: 10542

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56175 AN: 67970

Other (OTH) AF: 0.703 AC: 1484 AN: 2110

Alfa AF: 0.772 Hom.: 94447

Bravo AF: 0.688

Asia WGS AF: 0.370 AC: 1288 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.58
PhyloP100		0.024
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: rs537681; hg19: chr11-100988034;