13-114323923-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_032436.4(CHAMP1):c.81A>G(p.Glu27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00037 in 1,614,228 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (1 hom.)
• Consequence: CHAMP1 NM_032436.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.588

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 13-114323923-A-G is Benign according to our data. Variant chr13-114323923-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3040701.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.588 with no splicing effect.
• BS2: High AC in GnomAd at 57 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHAMP1	NM_032436.4	c.81A>G	p.Glu27=	synonymous_variant	3/3	ENST00000361283.4
CHAMP1	NM_001164144.3	c.81A>G	p.Glu27=	synonymous_variant	3/3
CHAMP1	NM_001164145.3	c.81A>G	p.Glu27=	synonymous_variant	3/3
CHAMP1	XM_047430277.1	c.81A>G	p.Glu27=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHAMP1	ENST00000361283.4	c.81A>G	p.Glu27=	synonymous_variant	3/3	1	NM_032436.4	P1

Frequencies

GnomAD3 genomes AF: 0.000374 AC: 57 AN: 152238 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000306 AC: 77 AN: 251436 Hom.: 0 AF XY: 0.000280 AC XY: 38 AN XY: 135894

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000510

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000369 AC: 540 AN: 1461872 Hom.: 1 Cov.: 31 AF XY: 0.000360 AC XY: 262 AN XY: 727234

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000449

Gnomad4 OTH exome AF: 0.000298

GnomAD4 genome AF: 0.000374 AC: 57 AN: 152356 Hom.: 0 Cov.: 32 AF XY: 0.000416 AC XY: 31 AN XY: 74500

Gnomad4 AFR AF: 0.000216

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000559

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000442 Hom.: 0

Bravo AF: 0.000404

EpiCase AF: 0.000273

EpiControl AF: 0.000533

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CHAMP1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 14, 2019

This variant is classified as likely 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	-0.55
Cadd	Benign	7.8
Dann	Benign	0.60

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

Other links and lift over

dbSNP: rs146349096; hg19: chr13-115089398;