rs7236739

Positions:

• chr18-23220751-A-G
• chr18-23220751-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001100619.3(CABLES1):​c.1088+6697A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,120 control chromosomes in the GnomAD database, including 7,377 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 0.30 (7377 hom., cov: 32)
• Consequence: CABLES1 NM_001100619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.80

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:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CABLES1	NM_001100619.3	c.1088+6697A>G		intron_variant		ENST00000256925.12	NP_001094089.1
CABLES1	NM_138375.3	c.293+6697A>G		intron_variant			NP_612384.1
CABLES1	NM_001256438.1	c.107+6697A>G		intron_variant			NP_001243367.1
CABLES1	NR_023359.2	n.331+6697A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CABLES1	ENST00000256925.12	c.1088+6697A>G		intron_variant		1	NM_001100619.3	ENSP00000256925.7

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45871 AN: 152002 Hom.: 7366 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.302 AC: 45923 AN: 152120 Hom.: 7377 Cov.: 32 AF XY: 0.303 AC XY: 22531 AN XY: 74368

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.325

Alfa AF: 0.301 Hom.: 3757

Bravo AF: 0.317

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.032
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs7236739; hg19: chr18-20800715;