6-126446454-C-T

Variant names:

• chr6-126446454-C-T
• rs1361108
• ENST00000651326.1:n.2417+26013G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000651326.1(ENSG00000293110):​n.2417+26013G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 149,892 control chromosomes in the GnomAD database, including 17,133 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 0.45 (17133 hom., cov: 28)
• Consequence: ENSG00000293110 ENST00000651326.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49
• Publications: 62 publications found

Genes affected

ENSG00000293110 (HGNC:):

CENPW (HGNC:21488): (centromere protein W) Predicted to enable DNA binding activity and protein heterodimerization activity. Involved in chromosome segregation; kinetochore assembly; and mitotic cell cycle. Located in kinetochore and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPW	NR_104462.2	n.474+12829C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000293110	ENST00000651326.1	n.2417+26013G>A		intron_variant	Intron 6 of 6
ENSG00000293110	ENST00000652383.1	n.630+85209G>A		intron_variant	Intron 3 of 4
ENSG00000307217	ENST00000824601.1	n.77+12829C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 68091 AN: 149774 Hom.: 17130 Cov.: 28

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.454 AC: 68118 AN: 149892 Hom.: 17133 Cov.: 28 AF XY: 0.464 AC XY: 33912 AN XY: 73130

African (AFR) AF: 0.292 AC: 11971 AN: 40998

American (AMR) AF: 0.621 AC: 9315 AN: 14988

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1638 AN: 3420

East Asian (EAS) AF: 0.974 AC: 4924 AN: 5054

South Asian (SAS) AF: 0.675 AC: 3198 AN: 4736

European-Finnish (FIN) AF: 0.436 AC: 4544 AN: 10424

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 30909 AN: 66996

Other (OTH) AF: 0.492 AC: 1020 AN: 2074

Alfa AF: 0.478 Hom.: 56912

Bravo AF: 0.465

Asia WGS AF: 0.706 AC: 2446 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.74
PhyloP100		2.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1361108; hg19: chr6-126767600;