11-101061074-A-G

Variant names:

• chr11-101061074-A-G
• rs545835
• NM_000926.4:c.2212+1373T>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.2212+1373T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,042 control chromosomes in the GnomAD database, including 16,389 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 0.44 (16389 hom., cov: 33)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 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.2212+1373T>C		intron	N/A	NP_000917.3
	PGR	NM_001202474.3		c.1720+1373T>C		intron	N/A	NP_001189403.1
	PGR	NM_001271161.2		c.1415-9506T>C		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.2212+1373T>C		intron	N/A	ENSP00000325120.5
	PGR	ENST00000263463.9	TSL:1	c.1907-9506T>C		intron	N/A	ENSP00000263463.5
	PGR	ENST00000526300.5	TSL:1	n.1907-9506T>C		intron	N/A	ENSP00000436803.1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66708 AN: 151924 Hom.: 16387 Cov.: 33

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.439 AC: 66733 AN: 152042 Hom.: 16389 Cov.: 33 AF XY: 0.448 AC XY: 33309 AN XY: 74304

African (AFR) AF: 0.212 AC: 8814 AN: 41512

American (AMR) AF: 0.503 AC: 7671 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1299 AN: 3470

East Asian (EAS) AF: 0.767 AC: 3963 AN: 5170

South Asian (SAS) AF: 0.642 AC: 3090 AN: 4814

European-Finnish (FIN) AF: 0.563 AC: 5942 AN: 10552

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34557 AN: 67954

Other (OTH) AF: 0.439 AC: 926 AN: 2110

Alfa AF: 0.467 Hom.: 2175

Bravo AF: 0.423

Asia WGS AF: 0.693 AC: 2399 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.59
PhyloP100		0.13
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: rs545835; hg19: chr11-100931805;