rs4800455

Variant names:

• chr18-23168769-A-G
• rs4800455
• NM_001100619.3:c.846-20069A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100619.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABLES1	NM_001100619.3	MANE Select	c.846-20069A>G		intron	N/A	NP_001094089.1	Q8TDN4-1
	CABLES1	NM_138375.3		c.50+12817A>G		intron	N/A	NP_612384.1	Q8TDN4-2
	CABLES1	NM_001256438.1		c.-136-20069A>G		intron	N/A	NP_001243367.1	Q8TDN4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABLES1	ENST00000256925.12	TSL:1 MANE Select	c.846-20069A>G		intron	N/A	ENSP00000256925.7	Q8TDN4-1
	CABLES1	ENST00000420687.2	TSL:1	c.50+12817A>G		intron	N/A	ENSP00000413851.2	Q8TDN4-2
	CABLES1	ENST00000877774.1		c.846-20069A>G		intron	N/A	ENSP00000547833.1

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

African (AFR) AF: 0.615 AC: 25505 AN: 41480

American (AMR) AF: 0.638 AC: 9744 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2880 AN: 3470

East Asian (EAS) AF: 0.799 AC: 4137 AN: 5178

South Asian (SAS) AF: 0.826 AC: 3981 AN: 4818

European-Finnish (FIN) AF: 0.776 AC: 8209 AN: 10584

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.801 AC: 54444 AN: 67984

Other (OTH) AF: 0.755 AC: 1597 AN: 2114

Alfa AF: 0.780 Hom.: 75284

Bravo AF: 0.715

Asia WGS AF: 0.809 AC: 2815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.077
DANN	Benign	0.15
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4800455; hg19: chr18-20748733;