rs3813133

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_032436.4(CHAMP1):c.876G>A(p.Pro292Pro) 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

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
intellectual disability, autosomal dominant 40
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CHAMP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CHAMP1	NM_032436.4 link	c.876G>A	p.Pro292Pro	synonymous_variant	Exon 3 of 3	ENST00000361283.4	NP_115812.1	Q96JM3
CHAMP1	NM_001164144.3 link	c.876G>A	p.Pro292Pro	synonymous_variant	Exon 3 of 3		NP_001157616.1	Q96JM3
CHAMP1	NM_001164145.3 link	c.876G>A	p.Pro292Pro	synonymous_variant	Exon 3 of 3		NP_001157617.1	Q96JM3
CHAMP1	XM_047430277.1 link	c.876G>A	p.Pro292Pro	synonymous_variant	Exon 3 of 3		XP_047286233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHAMP1	ENST00000361283.4 link	c.876G>A	p.Pro292Pro	synonymous_variant	Exon 3 of 3	1	NM_032436.4	ENSP00000354730.1		Q96JM3

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

GnomAD2 exomes

AF:

0.103

AC:

25736

AN:

251048

AF XY:

0.0977

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 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

African (AFR)

AF:

0.117

AC:

3919

AN:

33462

American (AMR)

AF:

0.198

AC:

8845

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

3015

AN:

26106

East Asian (EAS)

AF:

0.145

AC:

5765

AN:

39688

South Asian (SAS)

AF:

0.0966

AC:

8336

AN:

86252

European-Finnish (FIN)

AF:

0.0770

AC:

4112

AN:

53376

Middle Eastern (MID)

AF:

0.134

AC:

772

AN:

5766

European-Non Finnish (NFE)

AF:

0.0715

AC:

79483

AN:

1111740

Other (OTH)

AF:

0.0876

AC:

5288

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

7167

14333

21500

28666

35833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3106

6212

9318

12424

15530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0946

AC:

14382

AN:

151968

Hom.:

768

Cov.:

AF XY:

0.0968

AC XY:

7189

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.117

AC:

4856

AN:

41438

American (AMR)

AF:

0.142

AC:

2170

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

405

AN:

3466

East Asian (EAS)

AF:

0.118

AC:

611

AN:

5162

South Asian (SAS)

AF:

0.0970

AC:

467

AN:

4812

European-Finnish (FIN)

AF:

0.0792

AC:

836

AN:

10558

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0704

AC:

4782

AN:

67944

Other (OTH)

AF:

0.100

AC:

211

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

666

1332

1998

2664

3330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0837

Hom.:

2469

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

Mar 28, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.82

PhyloP100

-0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over