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GeneBe

11-101062676-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_000926.4(PGR):c.1983C>T(p.Gly661=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,613,730 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 7 hom. )

Consequence

PGR
NM_000926.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.00
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-101062676-G-A is Benign according to our data. Variant chr11-101062676-G-A is described in ClinVar as [Benign]. Clinvar id is 722198.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=3 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 221 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PGRNM_000926.4 linkuse as main transcriptc.1983C>T p.Gly661= synonymous_variant 4/8 ENST00000325455.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PGRENST00000325455.10 linkuse as main transcriptc.1983C>T p.Gly661= synonymous_variant 4/81 NM_000926.4 P1P06401-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00145
AC:
221
AN:
152058
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000828
Gnomad FIN
AF:
0.00444
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00244
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00137
AC:
343
AN:
250152
Hom.:
1
AF XY:
0.00121
AC XY:
163
AN XY:
135144
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.00486
Gnomad NFE exome
AF:
0.00192
Gnomad OTH exome
AF:
0.00164
GnomAD4 exome
AF:
0.00117
AC:
1708
AN:
1461554
Hom.:
7
Cov.:
31
AF XY:
0.00118
AC XY:
858
AN XY:
727104
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000510
Gnomad4 FIN exome
AF:
0.00603
Gnomad4 NFE exome
AF:
0.00115
Gnomad4 OTH exome
AF:
0.000960
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00145
AC:
221
AN:
152176
Hom.:
2
Cov.:
32
AF XY:
0.00148
AC XY:
110
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.0000964
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000829
Gnomad4 FIN
AF:
0.00444
Gnomad4 NFE
AF:
0.00244
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00220
Hom.:
2
Bravo
AF:
0.000676
EpiCase
AF:
0.00131
EpiControl
AF:
0.000711

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 submitterclinical testingInvitaeMay 24, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
Cadd
Benign
14
Dann
Benign
0.63

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs139646398; hg19: chr11-100933407; COSMIC: COSV99678728; API