rs11571171

Variant names:

• chr11-101104156-A-G
• rs11571171
• NM_000926.4:c.1790-12280T>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.1790-12280T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,186 control chromosomes in the GnomAD database, including 5,650 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 0.26 (5650 hom., cov: 33)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.31 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	NM_000926.4	MANE Select	c.1790-12280T>C		intron	N/A	NP_000917.3
	PGR	NM_001202474.3		c.1298-12280T>C		intron	N/A	NP_001189403.1
	PGR	NM_001271161.2		c.1298-12280T>C		intron	N/A	NP_001258090.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	ENST00000325455.10	TSL:1 MANE Select	c.1790-12280T>C		intron	N/A	ENSP00000325120.5
	PGR	ENST00000263463.9	TSL:1	c.1790-12280T>C		intron	N/A	ENSP00000263463.5
	PGR	ENST00000526300.5	TSL:1	n.1790-12280T>C		intron	N/A	ENSP00000436803.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40184 AN: 152068 Hom.: 5640 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.264 AC: 40220 AN: 152186 Hom.: 5650 Cov.: 33 AF XY: 0.261 AC XY: 19391 AN XY: 74376

African (AFR) AF: 0.192 AC: 7977 AN: 41548

American (AMR) AF: 0.263 AC: 4026 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1097 AN: 3472

East Asian (EAS) AF: 0.190 AC: 985 AN: 5184

South Asian (SAS) AF: 0.245 AC: 1181 AN: 4830

European-Finnish (FIN) AF: 0.258 AC: 2734 AN: 10584

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.314 AC: 21319 AN: 67970

Other (OTH) AF: 0.274 AC: 579 AN: 2114

Alfa AF: 0.281 Hom.: 782

Bravo AF: 0.262

Asia WGS AF: 0.163 AC: 567 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.28
DANN	Benign	0.41
PhyloP100		-1.7
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: rs11571171; hg19: chr11-100974887;