9-130714339-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_007313.3(ABL1):c.20A>G(p.Lys7Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,458,634 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ABL1
NM_007313.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 8.38

Publications

2 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABL1	NM_007313.3 link	c.20A>G	p.Lys7Arg	missense_variant	Exon 1 of 11		NP_009297.2	P00519-2Q59FK4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABL1	ENST00000372348.9 link	c.20A>G	p.Lys7Arg	missense_variant	Exon 1 of 11	1		ENSP00000361423.2		P00519-2
ABL1	ENST00000393293.4 link	c.20A>G	p.Lys7Arg	missense_variant	Exon 1 of 2	5		ENSP00000376971.4		R4GRW0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000200

AC:

AN:

249498

AF XY:

0.0000371

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1458634

Hom.:

Cov.:

AF XY:

0.00000965

AC XY:

AN XY:

725314

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33346

American (AMR)

AF:

0.00

AC:

AN:

44190

Ashkenazi Jewish (ASJ)

AF:

0.0000386

AC:

AN:

25922

East Asian (EAS)

AF:

0.00

AC:

AN:

39610

South Asian (SAS)

AF:

0.00

AC:

AN:

85994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

1110238

Other (OTH)

AF:

0.00

AC:

AN:

60218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Jun 06, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.20A>G (p.K7R) alteration is located in exon 1 (coding exon 1) of the ABL1 gene. This alteration results from a A to G substitution at nucleotide position 20, causing the lysine (K) at amino acid position 7 to be replaced by an arginine (R). The p.K7R alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Jan 16, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 7 of the ABL1 protein (p.Lys7Arg). This variant is present in population databases (rs375730000, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ABL1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ABL1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

.;T

Eigen

Benign

-0.10

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

D;D

MetaRNN

Uncertain

0.51

D;D

MetaSVM

Benign

-0.75

PhyloP100

8.4

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.60

N;N

REVEL

Uncertain

0.34

Sift

Benign

0.26

T;D

Sift4G

Benign

0.78

T;D

Vest4

0.45

MVP

0.86

MPC

0.64

ClinPred

0.92

GERP RS

5.6

PromoterAI

0.0024

Neutral

(source)

gMVP

0.62

Mutation Taster

=73/27

polymorphism

(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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9-130714339-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over