NM_000926.4:c.1790-6540C>T

Variant names:

• chr11-101098416-G-A
• rs491893
• NM_000926.4:c.1790-6540C>T

Variant summary

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

The NM_000926.4(PGR):​c.1790-6540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 151,974 control chromosomes in the GnomAD database, including 40,375 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 0.71 (40375 hom., cov: 31)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.821 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	NM_000926.4	MANE Select	c.1790-6540C>T		intron	N/A	NP_000917.3
	PGR	NM_001202474.3		c.1298-6540C>T		intron	N/A	NP_001189403.1
	PGR	NM_001271161.2		c.1298-6540C>T		intron	N/A	NP_001258090.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	ENST00000325455.10	TSL:1 MANE Select	c.1790-6540C>T		intron	N/A	ENSP00000325120.5
	PGR	ENST00000263463.9	TSL:1	c.1790-6540C>T		intron	N/A	ENSP00000263463.5
	PGR	ENST00000526300.5	TSL:1	n.1790-6540C>T		intron	N/A	ENSP00000436803.1

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108405 AN: 151858 Hom.: 40350 Cov.: 31

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.740

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.714 AC: 108473 AN: 151974 Hom.: 40375 Cov.: 31 AF XY: 0.707 AC XY: 52480 AN XY: 74264

African (AFR) AF: 0.593 AC: 24540 AN: 41414

American (AMR) AF: 0.681 AC: 10388 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2829 AN: 3468

East Asian (EAS) AF: 0.212 AC: 1092 AN: 5148

South Asian (SAS) AF: 0.535 AC: 2580 AN: 4818

European-Finnish (FIN) AF: 0.796 AC: 8414 AN: 10566

Middle Eastern (MID) AF: 0.731 AC: 212 AN: 290

European-Non Finnish (NFE) AF: 0.826 AC: 56190 AN: 67990

Other (OTH) AF: 0.711 AC: 1500 AN: 2110

Alfa AF: 0.764 Hom.: 5810

Bravo AF: 0.700

Asia WGS AF: 0.374 AC: 1306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.3
DANN	Benign	0.46
PhyloP100		0.36
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: rs491893; hg19: chr11-100969147;