11-101129639-C-G

Variant names:

• chr11-101129639-C-G
• rs2008112
• NM_000926.4:c.-569G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000926.4(PGR):​c.-569G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,148 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PGR NM_000926.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471
• 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]

PGR-AS1 (HGNC:52650): (PGR antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

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.-569G>C		5_prime_UTR	Exon 1 of 8	NP_000917.3	P06401-1
	PGR	NM_001271162.2		c.-357G>C		5_prime_UTR	Exon 1 of 8	NP_001258091.1	P06401-3
	PGR-AS1	NR_073144.1		n.563C>G		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	ENST00000325455.10	TSL:1 MANE Select	c.-569G>C		5_prime_UTR	Exon 1 of 8	ENSP00000325120.5	P06401-1
	PGR-AS1	ENST00000632820.1	TSL:1	n.563C>G		non_coding_transcript_exon	Exon 1 of 7
	PGR	ENST00000619228.2	TSL:5	c.-569G>C		5_prime_UTR	Exon 1 of 5	ENSP00000482698.1	Q8NG44

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 29878 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 13780

African (AFR) AF: 0.00 AC: 0 AN: 1026

American (AMR) AF: 0.00 AC: 0 AN: 668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1884

East Asian (EAS) AF: 0.00 AC: 0 AN: 5892

South Asian (SAS) AF: 0.00 AC: 0 AN: 244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 190

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 17548

Other (OTH) AF: 0.00 AC: 0 AN: 2408

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74324

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.7
DANN	Benign	0.66
PhyloP100		0.47
PromoterAI		-0.025	Neutral

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: rs2008112; hg19: chr11-101000370;