rs143837301

Positions:

chr9-130884406-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2

The NM_005157.6(ABL1):c.2116G>A(p.Gly706Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,612,018 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 14 hom. )

Consequence

ABL1
NM_005157.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 1.75

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ABL1. . Gene score misZ 2.5581 (greater than the threshold 3.09). Trascript score misZ 4.2755 (greater than threshold 3.09). GenCC has associacion of gene with congenital heart defects and skeletal malformations syndrome, connective tissue disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.003545463).

BP6

Variant 9-130884406-G-A is Benign according to our data. Variant chr9-130884406-G-A is described in ClinVar as [Benign]. Clinvar id is 133445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-130884406-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00193 (294/152340) while in subpopulation SAS AF= 0.006 (29/4830). AF 95% confidence interval is 0.00429. There are 0 homozygotes in gnomad4. There are 161 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 294 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABL1	NM_005157.6 linkuse as main transcript	c.2116G>A	p.Gly706Ser	missense_variant	11/11	ENST00000318560.6	NP_005148.2
ABL1	NM_007313.3 linkuse as main transcript	c.2173G>A	p.Gly725Ser	missense_variant	11/11		NP_009297.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABL1	ENST00000318560.6 linkuse as main transcript	c.2116G>A	p.Gly706Ser	missense_variant	11/11	1	NM_005157.6	ENSP00000323315		P00519-1
ABL1	ENST00000372348.9 linkuse as main transcript	c.2173G>A	p.Gly725Ser	missense_variant	11/11	1		ENSP00000361423	P1	P00519-2

Frequencies

GnomAD3 genomes

AF:

0.00192

AC:

293

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00225

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00254

AC:

623

AN:

245420

Hom.:

AF XY:

0.00281

AC XY:

376

AN XY:

133778

show subpopulations

Gnomad AFR exome

AF:

0.000651

Gnomad AMR exome

AF:

0.00230

Gnomad ASJ exome

AF:

0.00887

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00481

Gnomad FIN exome

AF:

0.00181

Gnomad NFE exome

AF:

0.00220

Gnomad OTH exome

AF:

0.00299

GnomAD4 exome

AF:

0.00237

AC:

3462

AN:

1459678

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

1809

AN XY:

726158

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00249

Gnomad4 ASJ exome

AF:

0.00927

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00415

Gnomad4 FIN exome

AF:

0.00159

Gnomad4 NFE exome

AF:

0.00218

Gnomad4 OTH exome

AF:

0.00307

GnomAD4 genome

AF:

0.00193

AC:

294

AN:

152340

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

161

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00835

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00600

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00226

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00263

Hom.:

Bravo

AF:

0.00181

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000910

AC:

ESP6500EA

AF:

0.00210

AC:

ExAC

AF:

0.00234

AC:

284

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1Other:1

not provided, no classification provided	reference population	ITMI	Sep 19, 2013	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.8

DANN

Benign

0.65

DEOGEN2

Benign

0.18

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.46

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.29

N;N

REVEL

Benign

0.024

Sift

Benign

1.0

T;T

Sift4G

Benign

0.83

T;T

Polyphen

0.0010

.;B

Vest4

0.089

MVP

0.23

MPC

0.21

ClinPred

0.00061

GERP RS

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.016

gMVP

0.076

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over