Variant 13-114324718-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_032436.4(CHAMP1):c.876G>A(p.Pro292=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.083 in 1,613,386 control chromosomes in the GnomAD database, including 6,368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.095 ( 768 hom., cov: 32)

Exomes 𝑓: 0.082 ( 5600 hom. )

Consequence

CHAMP1
NM_032436.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.597

Variant links:

Genes affected

CHAMP1 (HGNC:20311): (chromosome alignment maintaining phosphoprotein 1) This gene encodes a zinc finger protein that functions as a regulator of chromosome segregation in mitosis. The encoded protein is required for correct alignment of chromosomes on the metaphase plate, and plays a role in maintaining the attachment of sister kinetochores to microtubules from opposite spindle poles. Mutations in this gene are associated with an autosomal dominant form of intellectual disability. [provided by RefSeq, Jul 2017]

CHAMP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 13-114324718-G-A is Benign according to our data. Variant chr13-114324718-G-A is described in ClinVar as [Benign]. Clinvar id is 3059016.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.597 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CHAMP1	NM_032436.4 linkuse as main transcript	c.876G>A	p.Pro292=	synonymous_variant	3/3	ENST00000361283.4	NP_115812.1
CHAMP1	NM_001164144.3 linkuse as main transcript	c.876G>A	p.Pro292=	synonymous_variant	3/3		NP_001157616.1
CHAMP1	NM_001164145.3 linkuse as main transcript	c.876G>A	p.Pro292=	synonymous_variant	3/3		NP_001157617.1
CHAMP1	XM_047430277.1 linkuse as main transcript	c.876G>A	p.Pro292=	synonymous_variant	3/3		XP_047286233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHAMP1	ENST00000361283.4 linkuse as main transcript	c.876G>A	p.Pro292=	synonymous_variant	3/3	1	NM_032436.4	ENSP00000354730	P1

Frequencies

GnomAD3 genomes

AF:

0.0947

AC:

14375

AN:

151850

Hom.:

768

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.0974

Gnomad FIN

AF:

0.0792

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.0704

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.103

AC:

25736

AN:

251048

Hom.:

1629

AF XY:

0.0977

AC XY:

13259

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.104

Gnomad SAS exome

AF:

0.0981

Gnomad FIN exome

AF:

0.0784

Gnomad NFE exome

AF:

0.0738

Gnomad OTH exome

AF:

0.0992

GnomAD4 exome

AF:

0.0818

AC:

119535

AN:

1461418

Hom.:

5600

Cov.:

AF XY:

0.0817

AC XY:

59395

AN XY:

726980

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.198

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.145

Gnomad4 SAS exome

AF:

0.0966

Gnomad4 FIN exome

AF:

0.0770

Gnomad4 NFE exome

AF:

0.0715

Gnomad4 OTH exome

AF:

0.0876

GnomAD4 genome

AF:

0.0946

AC:

14382

AN:

151968

Hom.:

768

Cov.:

AF XY:

0.0968

AC XY:

7189

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.142

Gnomad4 ASJ

AF:

0.117

Gnomad4 EAS

AF:

0.118

Gnomad4 SAS

AF:

0.0970

Gnomad4 FIN

AF:

0.0792

Gnomad4 NFE

AF:

0.0704

Gnomad4 OTH

AF:

0.100

Alfa

AF:

0.0815

Hom.:

1119

Bravo

AF:

0.102

Asia WGS

AF:

0.0990

AC:

344

AN:

3478

EpiCase

AF:

0.0768

EpiControl

AF:

0.0744

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CHAMP1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

8.1

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

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