dbSNP rs7457: ABL1:c.*1756C>T (chr9-130887439-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 NM_005157.6(ABL1):c.*1756C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0997 in 233,244 control chromosomes in the GnomAD database, including 1,814 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 0.11 ( 1449 hom., cov: 33)

Exomes 𝑓: 0.075 ( 365 hom. )

Consequence

ABL1
NM_005157.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.92

Publications

12 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=-0.55).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABL1	NM_005157.6 link	c.*1756C>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000318560.6	NP_005148.2	P00519-1A0A024R8E2Q59FK4
ABL1	NM_007313.3 link	c.*1756C>T		3_prime_UTR_variant	Exon 11 of 11		NP_009297.2	P00519-2Q59FK4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABL1	ENST00000318560.6 link	c.*1756C>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_005157.6	ENSP00000323315.5		P00519-1
ABL1	ENST00000372348.9 link	c.*1756C>T		3_prime_UTR_variant	Exon 11 of 11	1		ENSP00000361423.2		P00519-2

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17125

AN:

152044

Hom.:

1446

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.0791

Gnomad ASJ

AF:

0.0628

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0268

Gnomad FIN

AF:

0.0322

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0768

Gnomad OTH

AF:

0.101

GnomAD4 exome

AF:

0.0754

AC:

6114

AN:

81082

Hom.:

365

Cov.:

AF XY:

0.0739

AC XY:

2756

AN XY:

37296

show subpopulations

African (AFR)

AF:

0.246

AC:

956

AN:

3892

American (AMR)

AF:

0.0757

AC:

189

AN:

2496

Ashkenazi Jewish (ASJ)

AF:

0.0658

AC:

337

AN:

5122

East Asian (EAS)

AF:

0.0000878

AC:

AN:

11394

South Asian (SAS)

AF:

0.0171

AC:

AN:

702

European-Finnish (FIN)

AF:

0.0284

AC:

AN:

282

Middle Eastern (MID)

AF:

0.0955

AC:

AN:

492

European-Non Finnish (NFE)

AF:

0.0790

AC:

3944

AN:

49942

Other (OTH)

AF:

0.0917

AC:

620

AN:

6760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

287

573

860

1146

1433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.113

AC:

17145

AN:

152162

Hom.:

1449

Cov.:

AF XY:

0.106

AC XY:

7921

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.235

AC:

9734

AN:

41480

American (AMR)

AF:

0.0789

AC:

1206

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0628

AC:

218

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5178

South Asian (SAS)

AF:

0.0268

AC:

129

AN:

4816

European-Finnish (FIN)

AF:

0.0322

AC:

341

AN:

10600

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0768

AC:

5226

AN:

68012

Other (OTH)

AF:

0.0995

AC:

210

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

734

1468

2201

2935

3669

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<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:

0.0929

Hom.:

1127

Bravo

AF:

0.121

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over