rs499699

Variant names:

• chr11-101039401-T-C
• rs499699
• NM_000926.4:c.2647-130A>G

Variant summary

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

The NM_000926.4(PGR):​c.2647-130A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 700,522 control chromosomes in the GnomAD database, including 25,040 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 0.32 (8979 hom., cov: 32)
  • Exomes 𝑓: 0.23 (16061 hom.)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 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.2647-130A>G		intron	N/A	NP_000917.3
	PGR	NM_001202474.3		c.2155-130A>G		intron	N/A	NP_001189403.1
	PGR	NM_001271161.2		c.1849-130A>G		intron	N/A	NP_001258090.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	ENST00000325455.10	TSL:1 MANE Select	c.2647-130A>G		intron	N/A	ENSP00000325120.5
	PGR	ENST00000263463.9	TSL:1	c.2341-130A>G		intron	N/A	ENSP00000263463.5
	PGR	ENST00000526300.5	TSL:1	n.*122-130A>G		intron	N/A	ENSP00000436803.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48573 AN: 151628 Hom.: 8951 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.230 AC: 125960 AN: 548776 Hom.: 16061 AF XY: 0.224 AC XY: 65581 AN XY: 293302

African (AFR) AF: 0.514 AC: 7229 AN: 14054

American (AMR) AF: 0.258 AC: 6936 AN: 26840

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 6487 AN: 17252

East Asian (EAS) AF: 0.219 AC: 6825 AN: 31144

South Asian (SAS) AF: 0.123 AC: 6488 AN: 52798

European-Finnish (FIN) AF: 0.214 AC: 7628 AN: 35600

Middle Eastern (MID) AF: 0.233 AC: 519 AN: 2232

European-Non Finnish (NFE) AF: 0.224 AC: 76077 AN: 339698

Other (OTH) AF: 0.267 AC: 7771 AN: 29158

GnomAD4 genome AF: 0.321 AC: 48665 AN: 151746 Hom.: 8979 Cov.: 32 AF XY: 0.314 AC XY: 23302 AN XY: 74156

African (AFR) AF: 0.523 AC: 21638 AN: 41412

American (AMR) AF: 0.296 AC: 4503 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1356 AN: 3466

East Asian (EAS) AF: 0.222 AC: 1149 AN: 5176

South Asian (SAS) AF: 0.128 AC: 619 AN: 4826

European-Finnish (FIN) AF: 0.216 AC: 2282 AN: 10570

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16129 AN: 67766

Other (OTH) AF: 0.320 AC: 672 AN: 2102

Alfa AF: 0.295 Hom.: 990

Bravo AF: 0.337

Asia WGS AF: 0.199 AC: 694 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.61
PhyloP100		-0.68
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: rs499699; hg19: chr11-100910132; COSMIC: COSV54802512; COSMIC: COSV54802512;