chr18-23216694-T-G

Variant names:

• chr18-23216694-T-G
• rs8093359
• NM_001100619.3:c.1088+2640T>G

Variant summary

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

The NM_001100619.3(CABLES1):​c.1088+2640T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,124 control chromosomes in the GnomAD database, including 8,867 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 0.33 (8867 hom., cov: 32)
• Consequence: CABLES1 NM_001100619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• 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]

TMEM241 (HGNC:31723): (transmembrane protein 241) Predicted to enable antiporter activity. Predicted to be involved in carbohydrate transport and transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.475 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.1088+2640T>G		intron	N/A	NP_001094089.1	Q8TDN4-1
	CABLES1	NM_138375.3		c.293+2640T>G		intron	N/A	NP_612384.1	Q8TDN4-2
	CABLES1	NM_001256438.1		c.107+2640T>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.1088+2640T>G		intron	N/A	ENSP00000256925.7	Q8TDN4-1
	CABLES1	ENST00000420687.2	TSL:1	c.293+2640T>G		intron	N/A	ENSP00000413851.2	Q8TDN4-2
	CABLES1	ENST00000877774.1		c.1011-17914T>G		intron	N/A	ENSP00000547833.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50594 AN: 152006 Hom.: 8850 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.333 AC: 50657 AN: 152124 Hom.: 8867 Cov.: 32 AF XY: 0.335 AC XY: 24934 AN XY: 74376

African (AFR) AF: 0.267 AC: 11077 AN: 41524

American (AMR) AF: 0.484 AC: 7407 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1571 AN: 3470

East Asian (EAS) AF: 0.320 AC: 1659 AN: 5178

South Asian (SAS) AF: 0.328 AC: 1579 AN: 4808

European-Finnish (FIN) AF: 0.316 AC: 3336 AN: 10562

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22811 AN: 67966

Other (OTH) AF: 0.360 AC: 762 AN: 2114

Alfa AF: 0.353 Hom.: 13100

Bravo AF: 0.344

Asia WGS AF: 0.329 AC: 1144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.024
DANN	Benign	0.75
PhyloP100		-1.3
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: rs8093359; hg19: chr18-20796658;