11-101129639-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000926.4(PGR):​c.-569G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00637 in 182,142 control chromosomes in the GnomAD database, including 52 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 0.0070 (48 hom., cov: 31)
  • Exomes 𝑓: 0.0030 (4 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0589 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.-569G>A		5_prime_UTR	Exon 1 of 8	NP_000917.3	P06401-1
	PGR	NM_001271162.2		c.-357G>A		5_prime_UTR	Exon 1 of 8	NP_001258091.1	P06401-3
	PGR-AS1	NR_073144.1		n.563C>T		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>A		5_prime_UTR	Exon 1 of 8	ENSP00000325120.5	P06401-1
	PGR-AS1	ENST00000632820.1	TSL:1	n.563C>T		non_coding_transcript_exon	Exon 1 of 7
	PGR	ENST00000619228.2	TSL:5	c.-569G>A		5_prime_UTR	Exon 1 of 5	ENSP00000482698.1	Q8NG44

Frequencies

GnomAD3 genomes AF: 0.00699 AC: 1063 AN: 152148 Hom.: 48 Cov.: 31

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0619

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00368

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.00305 AC: 91 AN: 29876 Hom.: 4 Cov.: 0 AF XY: 0.00298 AC XY: 41 AN XY: 13780

African (AFR) AF: 0.000975 AC: 1 AN: 1026

American (AMR) AF: 0.0976 AC: 65 AN: 666

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

East Asian (EAS) AF: 0.00204 AC: 12 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: 0.000114 AC: 2 AN: 17548

Other (OTH) AF: 0.00457 AC: 11 AN: 2408

GnomAD4 genome AF: 0.00702 AC: 1069 AN: 152266 Hom.: 48 Cov.: 31 AF XY: 0.00724 AC XY: 539 AN XY: 74452

African (AFR) AF: 0.00147 AC: 61 AN: 41566

American (AMR) AF: 0.0622 AC: 952 AN: 15306

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

East Asian (EAS) AF: 0.00369 AC: 19 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68006

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.000140 Hom.: 0

Bravo AF: 0.0137

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	10
DANN	Benign	0.83
PhyloP100		0.47
PromoterAI		-0.023	Neutral
Mutation Taster		=299/1	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: rs2008112; hg19: chr11-101000370; COSMIC: COSV105041287; COSMIC: COSV105041287;