11-101091096-C-G

Variant names:

• chr11-101091096-C-G
• rs503362
• NM_000926.4:c.1906+664G>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.1906+664G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,114 control chromosomes in the GnomAD database, including 41,909 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 0.74 (41909 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 12 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 = 0.966 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.1906+664G>C		intron	N/A	NP_000917.3
	PGR	NM_001202474.3		c.1414+664G>C		intron	N/A	NP_001189403.1
	PGR	NM_001271161.2		c.1414+664G>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.1906+664G>C		intron	N/A	ENSP00000325120.5
	PGR	ENST00000263463.9	TSL:1	c.1906+664G>C		intron	N/A	ENSP00000263463.5
	PGR	ENST00000526300.5	TSL:1	n.1906+664G>C		intron	N/A	ENSP00000436803.1

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112432 AN: 151996 Hom.: 41857 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.742

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

GnomAD4 genome AF: 0.740 AC: 112539 AN: 152114 Hom.: 41909 Cov.: 32 AF XY: 0.745 AC XY: 55345 AN XY: 74336

African (AFR) AF: 0.686 AC: 28445 AN: 41486

American (AMR) AF: 0.788 AC: 12049 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2664 AN: 3468

East Asian (EAS) AF: 0.988 AC: 5116 AN: 5176

South Asian (SAS) AF: 0.766 AC: 3687 AN: 4816

European-Finnish (FIN) AF: 0.770 AC: 8139 AN: 10574

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 50034 AN: 67992

Other (OTH) AF: 0.744 AC: 1571 AN: 2112

Alfa AF: 0.737 Hom.: 5134

Bravo AF: 0.739

Asia WGS AF: 0.890 AC: 3092 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	0.14
DANN	Benign	0.37
PhyloP100		-1.4
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: rs503362; hg19: chr11-100961827;