chr18-23155444-T-C

Position:

• chr18-23155444-T-C

Variant summary

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

The NM_001100619.3(CABLES1):​c.845+18837T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,184 control chromosomes in the GnomAD database, including 46,581 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 0.78 (46581 hom., cov: 33)
• Consequence: CABLES1 NM_001100619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CABLES1	NM_001100619.3	c.845+18837T>C		intron_variant		ENST00000256925.12	NP_001094089.1
CABLES1	NM_001256438.1	c.-137+20774T>C		intron_variant			NP_001243367.1
CABLES1	NR_023359.2	n.88+20793T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CABLES1	ENST00000256925.12	c.845+18837T>C		intron_variant		1	NM_001100619.3	ENSP00000256925.7

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118648 AN: 152066 Hom.: 46543 Cov.: 33

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.874

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.792

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

GnomAD4 genome AF: 0.780 AC: 118740 AN: 152184 Hom.: 46581 Cov.: 33 AF XY: 0.779 AC XY: 57980 AN XY: 74396

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.874

Gnomad4 EAS AF: 0.835

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.777

Gnomad4 NFE AF: 0.792

Gnomad4 OTH AF: 0.792

Alfa AF: 0.800 Hom.: 75084

Bravo AF: 0.769

Asia WGS AF: 0.849 AC: 2951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.9
DANN	Benign	0.71

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: rs4369779; hg19: chr18-20735408;