4-67494976-T-C

Variant names:

• chr4-67494976-T-C
• rs2632453
• NM_001812.4:c.2185+183A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001812.4(CENPC):​c.2185+183A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 152,258 control chromosomes in the GnomAD database, including 63,045 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 0.91 (63045 hom., cov: 32)
• Consequence: CENPC NM_001812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418
• Publications: 2 publications found

Genes affected

CENPC (HGNC:1854): (centromere protein C) Centromere protein C 1 is a centromere autoantigen and a component of the inner kinetochore plate. The protein is required for maintaining proper kinetochore size and a timely transition to anaphase. A putative pseudogene exists on chromosome 12. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001812.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPC	NM_001812.4	MANE Select	c.2185+183A>G		intron	N/A	NP_001803.2
	CENPC	NM_001362481.2		c.2185+183A>G		intron	N/A	NP_001349410.1
	CENPC	NR_155754.2		n.2333+183A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPC	ENST00000273853.11	TSL:1 MANE Select	c.2185+183A>G		intron	N/A	ENSP00000273853.6
	CENPC	ENST00000506882.5	TSL:1	n.*909+183A>G		intron	N/A	ENSP00000426078.1
	CENPC	ENST00000510189.5	TSL:1	n.2333+183A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.908 AC: 138185 AN: 152140 Hom.: 62983 Cov.: 32

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.961

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.913

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.908 AC: 138303 AN: 152258 Hom.: 63045 Cov.: 32 AF XY: 0.913 AC XY: 67959 AN XY: 74454

African (AFR) AF: 0.830 AC: 34448 AN: 41524

American (AMR) AF: 0.948 AC: 14490 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 3187 AN: 3472

East Asian (EAS) AF: 0.937 AC: 4854 AN: 5180

South Asian (SAS) AF: 0.952 AC: 4594 AN: 4826

European-Finnish (FIN) AF: 0.961 AC: 10210 AN: 10622

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.932 AC: 63434 AN: 68026

Other (OTH) AF: 0.914 AC: 1933 AN: 2116

Alfa AF: 0.926 Hom.: 34797

Bravo AF: 0.903

Asia WGS AF: 0.952 AC: 3309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.2
DANN	Benign	0.79
PhyloP100		-0.42
Mutation Taster		=100/0	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: rs2632453; hg19: chr4-68360694;