Genetic Variant ENST00000372348.9:c.136+23723C>T (chr9-130738178-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000372348.9(ABL1):c.136+23723C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 151,948 control chromosomes in the GnomAD database, including 3,440 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 0.19 ( 3440 hom., cov: 31)

Consequence

ABL1
ENST00000372348.9 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.144

Publications

4 publications found

Variant links:

Genes affected

ABL1 (HGNC:76): (ABL proto-oncogene 1, non-receptor tyrosine kinase) This gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014]

ABL1 Gene-Disease associations (from GenCC):

congenital heart defects and skeletal malformations syndrome
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
connective tissue disorder
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
bone development disease
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ABL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABL1	NM_007313.3 link	c.136+23723C>T		intron_variant	Intron 1 of 10		NP_009297.2	P00519-2Q59FK4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABL1	ENST00000372348.9 link	c.136+23723C>T		intron_variant	Intron 1 of 10	1		ENSP00000361423.2		P00519-2
ABL1	ENST00000393293.4 link	c.136+23723C>T		intron_variant	Intron 1 of 1	5		ENSP00000376971.4		R4GRW0

Frequencies

GnomAD3 genomes

AF:

0.189

AC:

28700

AN:

151830

Hom.:

3443

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0522

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.373

Gnomad EAS

AF:

0.0915

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.239

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

GnomAD4 genome

AF:

0.189

AC:

28689

AN:

151948

Hom.:

3440

Cov.:

AF XY:

0.186

AC XY:

13848

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.0520

AC:

2155

AN:

41446

American (AMR)

AF:

0.198

AC:

3013

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

1294

AN:

3468

East Asian (EAS)

AF:

0.0917

AC:

475

AN:

5178

South Asian (SAS)

AF:

0.244

AC:

1170

AN:

4804

European-Finnish (FIN)

AF:

0.185

AC:

1944

AN:

10528

Middle Eastern (MID)

AF:

0.384

AC:

112

AN:

292

European-Non Finnish (NFE)

AF:

0.261

AC:

17729

AN:

67966

Other (OTH)

AF:

0.236

AC:

496

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1146

2293

3439

4586

5732

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

300

600

900

1200

1500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.164

Hom.:

650

Bravo

AF:

0.186

Asia WGS

AF:

0.147

AC:

515

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

2.3

(source)

DANN

Benign

0.33

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over