NM_000926.4:c.-700T>C

Variant names:

• chr11-101129770-A-G
• rs518162
• NM_000926.4:c.-700T>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.-700T>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 0.873 in 178,728 control chromosomes in the GnomAD database, including 69,008 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 0.86 (57540 hom., cov: 30)
  • Exomes 𝑓: 0.93 (11468 hom.)
• Consequence: PGR NM_000926.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635
• Publications: 20 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 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.-700T>C		5_prime_UTR	Exon 1 of 8	NP_000917.3	P06401-1
	PGR	NM_001271162.2		c.-488T>C		5_prime_UTR	Exon 1 of 8	NP_001258091.1	P06401-3
	PGR-AS1	NR_073144.1		n.694A>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.-700T>C		5_prime_UTR	Exon 1 of 8	ENSP00000325120.5	P06401-1
	PGR-AS1	ENST00000632820.1	TSL:1	n.694A>G		non_coding_transcript_exon	Exon 1 of 7
	PGR	ENST00000619228.2	TSL:5	c.-700T>C		5_prime_UTR	Exon 1 of 5	ENSP00000482698.1	Q8NG44

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131341 AN: 151978 Hom.: 57498 Cov.: 30

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.877

GnomAD4 exome AF: 0.926 AC: 24666 AN: 26630 Hom.: 11468 Cov.: 0 AF XY: 0.930 AC XY: 11354 AN XY: 12212

African (AFR) AF: 0.691 AC: 614 AN: 888

American (AMR) AF: 0.900 AC: 506 AN: 562

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 1603 AN: 1710

East Asian (EAS) AF: 0.982 AC: 5496 AN: 5594

South Asian (SAS) AF: 0.934 AC: 213 AN: 228

European-Finnish (FIN) AF: 1.00 AC: 22 AN: 22

Middle Eastern (MID) AF: 0.933 AC: 168 AN: 180

European-Non Finnish (NFE) AF: 0.921 AC: 14119 AN: 15326

Other (OTH) AF: 0.908 AC: 1925 AN: 2120

GnomAD4 genome AF: 0.864 AC: 131439 AN: 152098 Hom.: 57540 Cov.: 30 AF XY: 0.866 AC XY: 64418 AN XY: 74362

African (AFR) AF: 0.710 AC: 29459 AN: 41472

American (AMR) AF: 0.903 AC: 13795 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3255 AN: 3470

East Asian (EAS) AF: 0.990 AC: 5086 AN: 5138

South Asian (SAS) AF: 0.943 AC: 4551 AN: 4826

European-Finnish (FIN) AF: 0.906 AC: 9594 AN: 10594

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.924 AC: 62816 AN: 68008

Other (OTH) AF: 0.878 AC: 1853 AN: 2110

Alfa AF: 0.912 Hom.: 119757

Bravo AF: 0.858

Asia WGS AF: 0.951 AC: 3308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.62
PhyloP100		-0.64
PromoterAI		-0.0044	Neutral
Mutation Taster		=300/0	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: rs518162; hg19: chr11-101000501;