4-67470861-A-T

Variant names:

• chr4-67470861-A-T
• rs9312181
• NM_001812.4:c.*1744T>A

Variant summary

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

The NM_001812.4(CENPC):​c.*1744T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 151,988 control chromosomes in the GnomAD database, including 30,023 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 0.63 (30017 hom., cov: 32)
  • Exomes 𝑓: 0.62 (6 hom.)
• Consequence: CENPC NM_001812.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.874
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 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.*1744T>A		3_prime_UTR	Exon 19 of 19	NP_001803.2	Q03188-1
	CENPC	NM_001362481.2		c.*1744T>A		3_prime_UTR	Exon 19 of 19	NP_001349410.1
	CENPC	NR_155754.2		n.4842T>A		non_coding_transcript_exon	Exon 19 of 19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPC	ENST00000273853.11	TSL:1 MANE Select	c.*1744T>A		3_prime_UTR	Exon 19 of 19	ENSP00000273853.6	Q03188-1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95059 AN: 151844 Hom.: 29976 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.664

GnomAD4 exome AF: 0.615 AC: 16 AN: 26 Hom.: 6 Cov.: 0 AF XY: 0.611 AC XY: 11 AN XY: 18

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.611 AC: 11 AN: 18

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.626 AC: 95148 AN: 151962 Hom.: 30017 Cov.: 32 AF XY: 0.631 AC XY: 46831 AN XY: 74226

African (AFR) AF: 0.615 AC: 25482 AN: 41416

American (AMR) AF: 0.732 AC: 11188 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2195 AN: 3468

East Asian (EAS) AF: 0.812 AC: 4204 AN: 5178

South Asian (SAS) AF: 0.697 AC: 3358 AN: 4820

European-Finnish (FIN) AF: 0.568 AC: 5985 AN: 10542

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40616 AN: 67948

Other (OTH) AF: 0.667 AC: 1406 AN: 2108

Alfa AF: 0.601 Hom.: 3402

Bravo AF: 0.640

Asia WGS AF: 0.768 AC: 2670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.71
PhyloP100		0.87

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: rs9312181; hg19: chr4-68336579;