chr18-23141009-G-T

Position:

• chr18-23141009-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000256925.12(CABLES1):​c.845+4402G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,104 control chromosomes in the GnomAD database, including 14,303 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 0.42 (14303 hom., cov: 32)
• Consequence: CABLES1 ENST00000256925.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638

Genes affected

CABLES1 (HGNC:25097): (Cdk5 and Abl enzyme substrate 1) This gene encodes a protein involved in regulation of the cell cycle through interactions with several cyclin-dependent kinases. One study (PMID: 16177568) reported aberrant splicing of transcripts from this gene which results in removal of the cyclin binding domain only in human cancer cells, and reduction in gene expression was shown in colorectal cancers (PMID: 17982127).Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

CABLES1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CABLES1	NM_001100619.3	c.845+4402G>T		intron_variant		ENST00000256925.12	NP_001094089.1
CABLES1	NM_001256438.1	c.-137+6339G>T		intron_variant			NP_001243367.1
CABLES1	NR_023359.2	n.88+6358G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CABLES1	ENST00000256925.12	c.845+4402G>T		intron_variant		1	NM_001100619.3	ENSP00000256925.7

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63258 AN: 151984 Hom.: 14293 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.416 AC: 63308 AN: 152104 Hom.: 14303 Cov.: 32 AF XY: 0.414 AC XY: 30780 AN XY: 74328

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.421

Alfa AF: 0.479 Hom.: 29919

Bravo AF: 0.399

Asia WGS AF: 0.481 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs11082304; hg19: chr18-20720973;