rs4800455

Positions:

• chr18-23168769-A-G
• chr18-23168769-A-T

Variant summary

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

The NM_001100619.3(CABLES1):​c.846-20069A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,114 control chromosomes in the GnomAD database, including 41,558 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 0.73 (41558 hom., cov: 32)
• Consequence: CABLES1 NM_001100619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CABLES1	NM_001100619.3	c.846-20069A>G		intron_variant		ENST00000256925.12	NP_001094089.1
CABLES1	NM_001256438.1	c.-136-20069A>G		intron_variant			NP_001243367.1
CABLES1	NM_138375.3	c.50+12817A>G		intron_variant			NP_612384.1
CABLES1	NR_023359.2	n.89-20069A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CABLES1	ENST00000256925.12	c.846-20069A>G		intron_variant		1	NM_001100619.3	ENSP00000256925

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111482 AN: 151998 Hom.: 41553 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.733 AC: 111528 AN: 152114 Hom.: 41558 Cov.: 32 AF XY: 0.731 AC XY: 54366 AN XY: 74340

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.830

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.801

Gnomad4 OTH AF: 0.755

Alfa AF: 0.788 Hom.: 59971

Bravo AF: 0.715

Asia WGS AF: 0.809 AC: 2815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.077
DANN	Benign	0.15

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: rs4800455; hg19: chr18-20748733;