Menu
GeneBe

12-132848720-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001161346.2(CHFR):c.1497G>A(p.Ala499=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000765 in 1,582,164 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00048 ( 3 hom. )

Consequence

CHFR
NM_001161346.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.50
Variant links:
Genes affected
CHFR (HGNC:20455): (checkpoint with forkhead and ring finger domains) This gene encodes an E3 ubiquitin-protein ligase required for the maintenance of the antephase checkpoint that regulates cell cycle entry into mitosis and, therefore, may play a key role in cell cycle progression and tumorigenesis. The encoded protein has an N-terminal forkhead-associated domain, a central RING-finger domain, and a cysteine-rich C-terminal region. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Mar 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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=-0.74).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-132848720-C-T is Benign according to our data. Variant chr12-132848720-C-T is described in ClinVar as [Benign]. Clinvar id is 725004.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=-1.5 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 Homozygotes in GnomAdExome at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CHFRNM_001161346.2 linkuse as main transcriptc.1497G>A p.Ala499= synonymous_variant 13/18 ENST00000450056.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CHFRENST00000450056.7 linkuse as main transcriptc.1497G>A p.Ala499= synonymous_variant 13/182 NM_001161346.2 Q96EP1-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00342
AC:
521
AN:
152216
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0114
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00170
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00106
AC:
207
AN:
195636
Hom.:
2
AF XY:
0.000897
AC XY:
94
AN XY:
104820
show subpopulations
Gnomad AFR exome
AF:
0.0139
Gnomad AMR exome
AF:
0.000827
Gnomad ASJ exome
AF:
0.00122
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000400
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000119
Gnomad OTH exome
AF:
0.000196
GnomAD4 exome
AF:
0.000483
AC:
690
AN:
1429830
Hom.:
3
Cov.:
30
AF XY:
0.000421
AC XY:
298
AN XY:
708124
show subpopulations
Gnomad4 AFR exome
AF:
0.0134
Gnomad4 AMR exome
AF:
0.000721
Gnomad4 ASJ exome
AF:
0.00192
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000737
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000693
Gnomad4 OTH exome
AF:
0.00139
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00342
AC:
521
AN:
152334
Hom.:
1
Cov.:
32
AF XY:
0.00330
AC XY:
246
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.0114
Gnomad4 AMR
AF:
0.00170
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00164
Hom.:
2
Bravo
AF:
0.00399
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

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 09, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
Cadd
Benign
2.9
Dann
Benign
0.90
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs7975454; hg19: chr12-133425306; COSMIC: COSV99905106; COSMIC: COSV99905106; API