11-101039078-A-G

Variant names:

• chr11-101039078-A-G
• rs484389
• NM_000926.4:c.*38T>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.*38T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,551,512 control chromosomes in the GnomAD database, including 47,866 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 0.28 (6474 hom., cov: 32)
  • Exomes 𝑓: 0.24 (41392 hom.)
• Consequence: PGR NM_000926.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 23 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 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.*38T>C		3_prime_UTR	Exon 8 of 8	NP_000917.3	P06401-1
	PGR	NM_001202474.3		c.*38T>C		3_prime_UTR	Exon 8 of 8	NP_001189403.1	P06401-2
	PGR	NM_001271161.2		c.*38T>C		3_prime_UTR	Exon 7 of 7	NP_001258090.1	P06401

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	ENST00000325455.10	TSL:1 MANE Select	c.*38T>C		3_prime_UTR	Exon 8 of 8	ENSP00000325120.5	P06401-1
	PGR	ENST00000533207.5	TSL:1	n.2207T>C		non_coding_transcript_exon	Exon 5 of 5
	PGR	ENST00000534013.5	TSL:2	c.*38T>C		3_prime_UTR	Exon 8 of 8	ENSP00000436561.1	P06401-3

Frequencies

GnomAD3 genomes AF: 0.284 AC: 42987 AN: 151562 Hom.: 6455 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.293

GnomAD2 exomes AF: 0.241 AC: 59220 AN: 246110 AF XY: 0.232

Gnomad AFR exome AF: 0.385

Gnomad AMR exome AF: 0.266

Gnomad ASJ exome AF: 0.383

Gnomad EAS exome AF: 0.223

Gnomad FIN exome AF: 0.225

Gnomad NFE exome AF: 0.236

Gnomad OTH exome AF: 0.258

GnomAD4 exome AF: 0.238 AC: 333808 AN: 1399832 Hom.: 41392 Cov.: 23 AF XY: 0.234 AC XY: 163977 AN XY: 699824

African (AFR) AF: 0.386 AC: 12425 AN: 32152

American (AMR) AF: 0.263 AC: 11658 AN: 44270

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 9701 AN: 25572

East Asian (EAS) AF: 0.221 AC: 8654 AN: 39206

South Asian (SAS) AF: 0.129 AC: 10967 AN: 84946

European-Finnish (FIN) AF: 0.223 AC: 11708 AN: 52496

Middle Eastern (MID) AF: 0.236 AC: 1329 AN: 5640

European-Non Finnish (NFE) AF: 0.239 AC: 252303 AN: 1057320

Other (OTH) AF: 0.259 AC: 15063 AN: 58230

GnomAD4 genome AF: 0.284 AC: 43068 AN: 151680 Hom.: 6474 Cov.: 32 AF XY: 0.278 AC XY: 20616 AN XY: 74166

African (AFR) AF: 0.394 AC: 16306 AN: 41386

American (AMR) AF: 0.284 AC: 4320 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1338 AN: 3462

East Asian (EAS) AF: 0.222 AC: 1146 AN: 5162

South Asian (SAS) AF: 0.128 AC: 616 AN: 4828

European-Finnish (FIN) AF: 0.217 AC: 2296 AN: 10582

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16113 AN: 67736

Other (OTH) AF: 0.294 AC: 620 AN: 2108

Alfa AF: 0.266 Hom.: 6934

Bravo AF: 0.296

Asia WGS AF: 0.192 AC: 668 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.4
DANN	Benign	0.68
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs484389; hg19: chr11-100909809; COSMIC: COSV54809145; COSMIC: COSV54809145;