chr11-101120314-T-G

Variant names:

• chr11-101120314-T-G
• rs550778
• NM_000926.4:c.1789+5693A>C

Variant summary

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

The ENST00000325455.10(PGR):​c.1789+5693A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,102 control chromosomes in the GnomAD database, including 5,797 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 0.25 (5797 hom., cov: 33)
• Consequence: PGR ENST00000325455.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000325455.10. 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.1789+5693A>C		intron	N/A	NP_000917.3
	PGR	NM_001202474.3		c.1297+5693A>C		intron	N/A	NP_001189403.1
	PGR	NM_001271161.2		c.1297+5693A>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.1789+5693A>C		intron	N/A	ENSP00000325120.5
	PGR	ENST00000263463.9	TSL:1	c.1789+5693A>C		intron	N/A	ENSP00000263463.5
	PGR	ENST00000526300.5	TSL:1	n.1789+5693A>C		intron	N/A	ENSP00000436803.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38334 AN: 151982 Hom.: 5800 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.00577

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.252 AC: 38335 AN: 152102 Hom.: 5797 Cov.: 33 AF XY: 0.253 AC XY: 18833 AN XY: 74344

African (AFR) AF: 0.105 AC: 4362 AN: 41512

American (AMR) AF: 0.249 AC: 3808 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 767 AN: 3462

East Asian (EAS) AF: 0.00578 AC: 30 AN: 5190

South Asian (SAS) AF: 0.203 AC: 980 AN: 4826

European-Finnish (FIN) AF: 0.378 AC: 3987 AN: 10554

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23534 AN: 67960

Other (OTH) AF: 0.248 AC: 524 AN: 2110

Alfa AF: 0.288 Hom.: 908

Bravo AF: 0.236

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.75
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs550778; hg19: chr11-100991045;