6-126437887-G-T

Variant names:

• chr6-126437887-G-T
• rs9385399
• ENST00000651326.1:n.2417+34580C>A

Variant summary

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

The ENST00000651326.1(ENSG00000293110):​n.2417+34580C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,480 control chromosomes in the GnomAD database, including 16,619 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 0.44 (16619 hom., cov: 32)
• Consequence: ENSG00000293110 ENST00000651326.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 29 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• 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+4262G>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+34580C>A		intron_variant	Intron 6 of 6
ENSG00000293110	ENST00000652383.1	n.630+93776C>A		intron_variant	Intron 3 of 4
ENSG00000307217	ENST00000824601.1	n.77+4262G>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66157 AN: 151362 Hom.: 16618 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.437 AC: 66162 AN: 151480 Hom.: 16619 Cov.: 32 AF XY: 0.446 AC XY: 33041 AN XY: 74008

African (AFR) AF: 0.228 AC: 9436 AN: 41378

American (AMR) AF: 0.614 AC: 9314 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1658 AN: 3460

East Asian (EAS) AF: 0.975 AC: 5018 AN: 5148

South Asian (SAS) AF: 0.677 AC: 3256 AN: 4812

European-Finnish (FIN) AF: 0.435 AC: 4585 AN: 10546

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31299 AN: 67676

Other (OTH) AF: 0.476 AC: 998 AN: 2096

Alfa AF: 0.455 Hom.: 30630

Bravo AF: 0.444

Asia WGS AF: 0.693 AC: 2406 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.65
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs9385399; hg19: chr6-126759033; COSMIC: COSV60280140;