rs2008112

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-101129639-C-A
• chr11-101129639-C-G
• chr11-101129639-C-T

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>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PGR NM_000926.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471
• Publications: 0 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=-0.7).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.-569G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	ENST00000325455.10	NP_000917.3
PGR	NM_000926.4	c.-569G>T		5_prime_UTR_variant	Exon 1 of 8	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.-569G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	1	NM_000926.4	ENSP00000325120.5
PGR	ENST00000325455.10	c.-569G>T		5_prime_UTR_variant	Exon 1 of 8	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes Cov.: 31

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 Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.3
DANN	Benign	0.77
PhyloP100		0.47
PromoterAI		-0.024	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;