chr11-101096821-A-G

Variant names:

• chr11-101096821-A-G
• rs601040
• NM_000926.4:c.1790-4945T>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.1790-4945T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 152,176 control chromosomes in the GnomAD database, including 58,128 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 0.87 (58128 hom., cov: 33)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• Publications: 2 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 (EAS) allele frequency at 95% confidence interval = 0.968 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	NM_000926.4	MANE Select	c.1790-4945T>C		intron	N/A	NP_000917.3
	PGR	NM_001202474.3		c.1298-4945T>C		intron	N/A	NP_001189403.1
	PGR	NM_001271161.2		c.1298-4945T>C		intron	N/A	NP_001258090.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	ENST00000325455.10	TSL:1 MANE Select	c.1790-4945T>C		intron	N/A	ENSP00000325120.5
	PGR	ENST00000263463.9	TSL:1	c.1790-4945T>C		intron	N/A	ENSP00000263463.5
	PGR	ENST00000526300.5	TSL:1	n.1790-4945T>C		intron	N/A	ENSP00000436803.1

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132124 AN: 152058 Hom.: 58086 Cov.: 33

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.880

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

GnomAD4 genome AF: 0.869 AC: 132219 AN: 152176 Hom.: 58128 Cov.: 33 AF XY: 0.872 AC XY: 64857 AN XY: 74404

African (AFR) AF: 0.719 AC: 29834 AN: 41482

American (AMR) AF: 0.904 AC: 13825 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3254 AN: 3470

East Asian (EAS) AF: 0.990 AC: 5129 AN: 5180

South Asian (SAS) AF: 0.951 AC: 4587 AN: 4822

European-Finnish (FIN) AF: 0.925 AC: 9803 AN: 10600

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.925 AC: 62896 AN: 68014

Other (OTH) AF: 0.881 AC: 1864 AN: 2116

Alfa AF: 0.841 Hom.: 20303

Bravo AF: 0.861

Asia WGS AF: 0.958 AC: 3332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.0
DANN	Benign	0.20
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs601040; hg19: chr11-100967552;