Variant 11-101125999-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000926.4(PGR):c.1789+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 1,612,912 control chromosomes in the GnomAD database, including 241 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0095 ( 10 hom., cov: 33)

Exomes 𝑓: 0.016 ( 231 hom. )

Consequence

PGR
NM_000926.4 splice_region, intron

Scores

Splicing: ADA: 0.0001037

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0110

Variant links:

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]

PGR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-101125999-G-A is Benign according to our data. Variant chr11-101125999-G-A is described in ClinVar as [Benign]. Clinvar id is 785890.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00955 (1453/152218) while in subpopulation NFE AF= 0.0171 (1163/68004). AF 95% confidence interval is 0.0163. There are 10 homozygotes in gnomad4. There are 616 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1453 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGR	NM_000926.4 linkuse as main transcript	c.1789+8C>T		splice_region_variant, intron_variant		ENST00000325455.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGR	ENST00000325455.10 linkuse as main transcript	c.1789+8C>T		splice_region_variant, intron_variant		1	NM_000926.4	P1	P06401-1

Frequencies

GnomAD3 genomes

AF:

0.00955

AC:

1452

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00609

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00498

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0171

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00954

AC:

2398

AN:

251414

Hom.:

AF XY:

0.00977

AC XY:

1328

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00357

Gnomad AMR exome

AF:

0.00529

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00503

Gnomad FIN exome

AF:

0.00397

Gnomad NFE exome

AF:

0.0164

Gnomad OTH exome

AF:

0.00879

GnomAD4 exome

AF:

0.0162

AC:

23676

AN:

1460694

Hom.:

231

Cov.:

AF XY:

0.0159

AC XY:

11587

AN XY:

726728

show subpopulations

Gnomad4 AFR exome

AF:

0.00254

Gnomad4 AMR exome

AF:

0.00557

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00554

Gnomad4 FIN exome

AF:

0.00455

Gnomad4 NFE exome

AF:

0.0195

Gnomad4 OTH exome

AF:

0.0146

GnomAD4 genome

AF:

0.00955

AC:

1453

AN:

152218

Hom.:

Cov.:

AF XY:

0.00828

AC XY:

616

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00284

Gnomad4 AMR

AF:

0.00608

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00519

Gnomad4 FIN

AF:

0.00349

Gnomad4 NFE

AF:

0.0171

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.0133

Hom.:

Bravo

AF:

0.00961

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0139

EpiControl

AF:

0.0156

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.9

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over