rs3813131

chr13-114324544-G-Achr13-114324544-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032436.4(CHAMP1):c.702G>A(p.Pro234=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 1,613,838 control chromosomes in the GnomAD database, including 10,694 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2462 hom., cov: 32)
  • Exomes 𝑓: 0.093 (8232 hom.)
• Consequence: CHAMP1 NM_032436.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-1.44 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHAMP1	NM_032436.4	c.702G>A	p.Pro234=	synonymous_variant	3/3	ENST00000361283.4
CHAMP1	NM_001164144.3	c.702G>A	p.Pro234=	synonymous_variant	3/3
CHAMP1	NM_001164145.3	c.702G>A	p.Pro234=	synonymous_variant	3/3
CHAMP1	XM_047430277.1	c.702G>A	p.Pro234=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHAMP1	ENST00000361283.4	c.702G>A	p.Pro234=	synonymous_variant	3/3	1	NM_032436.4	P1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23103 AN: 151834 Hom.: 2455 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0830

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0749

Gnomad OTH AF: 0.150

GnomAD3 exomes AF: 0.126 AC: 31622 AN: 251438 Hom.: 2654 AF XY: 0.119 AC XY: 16227 AN XY: 135902

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.219

Gnomad ASJ exome AF: 0.128

Gnomad EAS exome AF: 0.106

Gnomad SAS exome AF: 0.146

Gnomad FIN exome AF: 0.0812

Gnomad NFE exome AF: 0.0780

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.0935 AC: 136656 AN: 1461886 Hom.: 8232 Cov.: 32 AF XY: 0.0940 AC XY: 68371 AN XY: 727248

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.215

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.146

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.0796

Gnomad4 NFE exome AF: 0.0748

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.152 AC: 23144 AN: 151952 Hom.: 2462 Cov.: 32 AF XY: 0.152 AC XY: 11302 AN XY: 74282

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.0830

Gnomad4 NFE AF: 0.0749

Gnomad4 OTH AF: 0.151

Alfa AF: 0.0967 Hom.: 1948

Bravo AF: 0.165

Asia WGS AF: 0.167 AC: 580 AN: 3478

EpiCase AF: 0.0816

EpiControl AF: 0.0805

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.6
Dann	Benign	0.36
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

Other links and lift over

dbSNP: rs3813131; hg19: chr13-115090019; COSMIC: COSV63522367; COSMIC: COSV63522367;