rs4800148

Variant names:

• chr18-23144364-G-A
• rs4800148
• NM_001100619.3:c.845+7757G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-23144364-G-A
• chr18-23144364-G-C

Variant summary

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

The NM_001100619.3(CABLES1):​c.845+7757G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,172 control chromosomes in the GnomAD database, including 43,128 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 0.75 (43128 hom., cov: 33)
• Consequence: CABLES1 NM_001100619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• Publications: 51 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.787 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.845+7757G>A		intron	N/A	NP_001094089.1	Q8TDN4-1
	CABLES1	NM_001256438.1		c.-137+9694G>A		intron	N/A	NP_001243367.1	Q8TDN4-4
	CABLES1	NR_023359.2		n.88+9713G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABLES1	ENST00000256925.12	TSL:1 MANE Select	c.845+7757G>A		intron	N/A	ENSP00000256925.7	Q8TDN4-1
	CABLES1	ENST00000877774.1		c.845+7757G>A		intron	N/A	ENSP00000547833.1
	CABLES1	ENST00000952329.1		c.845+7757G>A		intron	N/A	ENSP00000622388.1

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114150 AN: 152054 Hom.: 43124 Cov.: 33

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.750 AC: 114196 AN: 152172 Hom.: 43128 Cov.: 33 AF XY: 0.748 AC XY: 55680 AN XY: 74402

African (AFR) AF: 0.711 AC: 29504 AN: 41514

American (AMR) AF: 0.639 AC: 9770 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2903 AN: 3472

East Asian (EAS) AF: 0.755 AC: 3906 AN: 5176

South Asian (SAS) AF: 0.808 AC: 3898 AN: 4826

European-Finnish (FIN) AF: 0.765 AC: 8099 AN: 10586

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.786 AC: 53455 AN: 68002

Other (OTH) AF: 0.772 AC: 1627 AN: 2108

Alfa AF: 0.779 Hom.: 203884

Bravo AF: 0.738

Asia WGS AF: 0.786 AC: 2734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.058
DANN	Benign	0.36
PhyloP100		-2.7
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: rs4800148; hg19: chr18-20724328;