Variant 12-132848720-C-T details in Genebe, Genetics Data Aggregator

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.Ala499Ala) 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

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]

CHFR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

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

Synonymous conserved (PhyloP=-1.5 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHFR	NM_001161346.2 link	c.1497G>A	p.Ala499Ala	synonymous_variant	13/18	ENST00000450056.7	NP_001154818.1	Q96EP1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHFR	ENST00000450056.7 link	c.1497G>A	p.Ala499Ala	synonymous_variant	13/18	2	NM_001161346.2	ENSP00000398735.2		Q96EP1-2
CHFR	ENST00000315585.11 link	n.933G>A		non_coding_transcript_exon_variant	11/16	2		ENSP00000320557.8		A0A096P6K8

Frequencies

GnomAD3 genomes

AF:

0.00342

AC:

521

AN:

152216

Hom.:

Cov.:

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.:

AF XY:

0.000897

AC XY:

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.:

Cov.:

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

AF:

0.00342

AC:

521

AN:

152334

Hom.:

Cov.:

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.:

Bravo

AF:

0.00399

Asia WGS

AF:

0.000866

AC:

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 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.

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