chr18-23135987-C-T

Variant names:

• chr18-23135987-C-T
• rs375018617
• NM_001100619.3:c.225C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001100619.3(CABLES1):​c.225C>T​(p.Asp75Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,138,040 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (4 hom.)
• Consequence: CABLES1 NM_001100619.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.481
• Publications: 4 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 18-23135987-C-T is Benign according to our data. Variant chr18-23135987-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 779177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.481 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 4 gene

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.225C>T	p.Asp75Asp	synonymous	Exon 1 of 10	NP_001094089.1	Q8TDN4-1
	CABLES1	NM_001256438.1		c.-137+1317C>T		intron	N/A	NP_001243367.1	Q8TDN4-4
	CABLES1	NR_023359.2		n.88+1336C>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.225C>T	p.Asp75Asp	synonymous	Exon 1 of 10	ENSP00000256925.7	Q8TDN4-1
	CABLES1	ENST00000877774.1		c.225C>T	p.Asp75Asp	synonymous	Exon 1 of 9	ENSP00000547833.1
	CABLES1	ENST00000952329.1		c.225C>T	p.Asp75Asp	synonymous	Exon 1 of 9	ENSP00000622388.1

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 212 AN: 148268 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000195

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.00147

Gnomad ASJ AF: 0.000881

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00250

Gnomad OTH AF: 0.00293

GnomAD2 exomes AF: 0.00199 AC: 54 AN: 27112 AF XY: 0.00265

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000441

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00298

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00225 AC: 2225 AN: 989664 Hom.: 4 Cov.: 30 AF XY: 0.00233 AC XY: 1090 AN XY: 468616

African (AFR) AF: 0.000198 AC: 4 AN: 20232

American (AMR) AF: 0.00217 AC: 16 AN: 7374

Ashkenazi Jewish (ASJ) AF: 0.000401 AC: 4 AN: 9974

East Asian (EAS) AF: 0.00 AC: 0 AN: 16430

South Asian (SAS) AF: 0.000797 AC: 16 AN: 20068

European-Finnish (FIN) AF: 0.000131 AC: 2 AN: 15270

Middle Eastern (MID) AF: 0.000414 AC: 1 AN: 2414

European-Non Finnish (NFE) AF: 0.00248 AC: 2135 AN: 861498

Other (OTH) AF: 0.00129 AC: 47 AN: 36404

GnomAD4 genome AF: 0.00143 AC: 212 AN: 148376 Hom.: 0 Cov.: 32 AF XY: 0.00116 AC XY: 84 AN XY: 72298

African (AFR) AF: 0.000194 AC: 8 AN: 41172

American (AMR) AF: 0.00147 AC: 22 AN: 14942

Ashkenazi Jewish (ASJ) AF: 0.000881 AC: 3 AN: 3406

East Asian (EAS) AF: 0.00 AC: 0 AN: 5088

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9198

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00250 AC: 166 AN: 66476

Other (OTH) AF: 0.00290 AC: 6 AN: 2068

Alfa AF: 0.00148 Hom.: 0

Bravo AF: 0.00159

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Uncertain	0.98
PhyloP100		0.48
PromoterAI		0.080	Neutral
Mutation Taster		=100/0	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: rs375018617; hg19: chr18-20715951; COSMIC: COSV56934590; COSMIC: COSV56934590;