rs920622592

Variant names:

• chr18-23136073-C-T
• rs920622592
• NM_001100619.3:c.311C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-23136073-C-T
• chr18-23136073-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001100619.3(CABLES1):​c.311C>T​(p.Ala104Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,167,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: CABLES1 NM_001100619.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.412
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049378455).

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.311C>T	p.Ala104Val	missense	Exon 1 of 10	NP_001094089.1	Q8TDN4-1
	CABLES1	NM_001256438.1		c.-137+1403C>T		intron	N/A	NP_001243367.1	Q8TDN4-4
	CABLES1	NR_023359.2		n.88+1422C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABLES1	ENST00000256925.12	TSL:1 MANE Select	c.311C>T	p.Ala104Val	missense	Exon 1 of 10	ENSP00000256925.7	Q8TDN4-1
	CABLES1	ENST00000877774.1		c.311C>T	p.Ala104Val	missense	Exon 1 of 9	ENSP00000547833.1
	CABLES1	ENST00000952329.1		c.311C>T	p.Ala104Val	missense	Exon 1 of 9	ENSP00000622388.1

Frequencies

GnomAD3 genomes AF: 0.0000402 AC: 6 AN: 149294 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 966 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000688 AC: 7 AN: 1017898 Hom.: 0 Cov.: 32 AF XY: 0.0000104 AC XY: 5 AN XY: 480872

African (AFR) AF: 0.000146 AC: 3 AN: 20550

American (AMR) AF: 0.00 AC: 0 AN: 6222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11414

East Asian (EAS) AF: 0.00 AC: 0 AN: 20084

South Asian (SAS) AF: 0.00 AC: 0 AN: 19206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18336

Middle Eastern (MID) AF: 0.000387 AC: 1 AN: 2584

European-Non Finnish (NFE) AF: 0.00000341 AC: 3 AN: 880844

Other (OTH) AF: 0.00 AC: 0 AN: 38658

GnomAD4 genome AF: 0.0000402 AC: 6 AN: 149400 Hom.: 0 Cov.: 32 AF XY: 0.0000412 AC XY: 3 AN XY: 72892

African (AFR) AF: 0.000146 AC: 6 AN: 41224

American (AMR) AF: 0.00 AC: 0 AN: 15036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 5104

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66954

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000718

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.41
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.049
Sift	Benign	0.30	T
Sift4G	Benign	0.26	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.28		Loss of disorder (P = 0.085)
MVP		0.34
MPC		1.2
ClinPred		0.33	T
GERP RS		-0.50
PromoterAI		0.018	Neutral
Varity_R		0.036
gMVP		0.32
Mutation Taster		=95/5	polymorphism

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: rs920622592; hg19: chr18-20716037;