rs635984

Variant names:

• chr11-101052435-C-G
• rs635984
• NM_000926.4:c.2213-867G>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.2213-867G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,776 control chromosomes in the GnomAD database, including 15,793 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 0.43 (15793 hom., cov: 30)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.2213-867G>C		intron_variant	Intron 4 of 7	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.2213-867G>C		intron_variant	Intron 4 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65334 AN: 151662 Hom.: 15793 Cov.: 30

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.431 AC: 65356 AN: 151776 Hom.: 15793 Cov.: 30 AF XY: 0.441 AC XY: 32682 AN XY: 74126

African (AFR) AF: 0.210 AC: 8694 AN: 41386

American (AMR) AF: 0.497 AC: 7567 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1290 AN: 3464

East Asian (EAS) AF: 0.775 AC: 3974 AN: 5128

South Asian (SAS) AF: 0.640 AC: 3074 AN: 4804

European-Finnish (FIN) AF: 0.562 AC: 5917 AN: 10520

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.493 AC: 33474 AN: 67932

Other (OTH) AF: 0.431 AC: 910 AN: 2112

Alfa AF: 0.462 Hom.: 2362

Bravo AF: 0.414

Asia WGS AF: 0.701 AC: 2432 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	0.095
DANN	Benign	0.56
PhyloP100		-1.2
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: rs635984; hg19: chr11-100923166;