rs3813131

Variant names:

• chr13-114324544-G-A
• rs3813131
• NM_032436.4:c.702G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-114324544-G-A
• chr13-114324544-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032436.4(CHAMP1):​c.702G>A​(p.Pro234Pro) 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
• Publications: 18 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CHAMP1	NM_032436.4	c.702G>A	p.Pro234Pro	synonymous_variant	Exon 3 of 3	ENST00000361283.4	NP_115812.1
CHAMP1	NM_001164144.3	c.702G>A	p.Pro234Pro	synonymous_variant	Exon 3 of 3		NP_001157616.1
CHAMP1	NM_001164145.3	c.702G>A	p.Pro234Pro	synonymous_variant	Exon 3 of 3		NP_001157617.1
CHAMP1	XM_047430277.1	c.702G>A	p.Pro234Pro	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	c.702G>A	p.Pro234Pro	synonymous_variant	Exon 3 of 3	1	NM_032436.4	ENSP00000354730.1

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

GnomAD2 exomes AF: 0.126 AC: 31622 AN: 251438 AF XY: 0.119

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 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

African (AFR) AF: 0.306 AC: 10237 AN: 33480

American (AMR) AF: 0.215 AC: 9607 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 3440 AN: 26136

East Asian (EAS) AF: 0.146 AC: 5794 AN: 39700

South Asian (SAS) AF: 0.145 AC: 12506 AN: 86256

European-Finnish (FIN) AF: 0.0796 AC: 4251 AN: 53418

Middle Eastern (MID) AF: 0.166 AC: 959 AN: 5768

European-Non Finnish (NFE) AF: 0.0748 AC: 83198 AN: 1112008

Other (OTH) AF: 0.110 AC: 6664 AN: 60396

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

African (AFR) AF: 0.298 AC: 12351 AN: 41394

American (AMR) AF: 0.172 AC: 2627 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 466 AN: 3472

East Asian (EAS) AF: 0.120 AC: 616 AN: 5146

South Asian (SAS) AF: 0.149 AC: 719 AN: 4818

European-Finnish (FIN) AF: 0.0830 AC: 878 AN: 10578

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0749 AC: 5093 AN: 67968

Other (OTH) AF: 0.151 AC: 319 AN: 2108

Alfa AF: 0.109 Hom.: 4089

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
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

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