11-101034978-T-G

Position:

• chr11-101034978-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000926.4(PGR):​c.*4138A>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 0.282 in 193,660 control chromosomes in the GnomAD database, including 7,971 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 0.29 (6454 hom., cov: 33)
  • Exomes 𝑓: 0.27 (1517 hom.)
• Consequence: PGR NM_000926.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGR	NM_000926.4	c.*4138A>C		3_prime_UTR_variant	8/8	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.*4138A>C		3_prime_UTR_variant	8/8	1	NM_000926.4	ENSP00000325120	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43317 AN: 151952 Hom.: 6436 Cov.: 33

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.270 AC: 11238 AN: 41590 Hom.: 1517 Cov.: 0 AF XY: 0.271 AC XY: 5205 AN XY: 19206

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.234

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.0909

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.285 AC: 43392 AN: 152070 Hom.: 6454 Cov.: 33 AF XY: 0.279 AC XY: 20758 AN XY: 74354

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.306

Alfa AF: 0.272 Hom.: 742

Bravo AF: 0.298

Asia WGS AF: 0.199 AC: 694 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs473409; hg19: chr11-100905709;