rs7106686

Variant names:

• chr11-101112367-G-A
• rs7106686
• NM_000926.4:c.1789+13640C>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.1789+13640C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 151,996 control chromosomes in the GnomAD database, including 3,254 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 0.19 (3254 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1789+13640C>T		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+13640C>T		intron_variant	Intron 2 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28457 AN: 151878 Hom.: 3230 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.0642

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.188 AC: 28532 AN: 151996 Hom.: 3254 Cov.: 32 AF XY: 0.184 AC XY: 13645 AN XY: 74304

African (AFR) AF: 0.323 AC: 13383 AN: 41414

American (AMR) AF: 0.170 AC: 2602 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 605 AN: 3468

East Asian (EAS) AF: 0.191 AC: 982 AN: 5154

South Asian (SAS) AF: 0.0649 AC: 313 AN: 4822

European-Finnish (FIN) AF: 0.104 AC: 1103 AN: 10574

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.133 AC: 9041 AN: 67984

Other (OTH) AF: 0.173 AC: 365 AN: 2112

Alfa AF: 0.170 Hom.: 449

Bravo AF: 0.200

Asia WGS AF: 0.134 AC: 464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.75
DANN	Benign	0.47
PhyloP100		-0.16
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: rs7106686; hg19: chr11-100983098;