9-130884719-C-T

Position:

chr9-130884719-C-T

Variant summary

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

The ENST00000318560.6(ABL1):c.2429C>T(p.Pro810Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00655 in 1,612,558 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0048 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0067 ( 44 hom. )

Consequence

ABL1
ENST00000318560.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 7.65

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=0.008353174).

BP6

Variant 9-130884719-C-T is Benign according to our data. Variant chr9-130884719-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 133440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0048 (731/152278) while in subpopulation NFE AF= 0.00754 (513/68016). AF 95% confidence interval is 0.007. There are 2 homozygotes in gnomad4. There are 343 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 731 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABL1	NM_005157.6 linkuse as main transcript	c.2429C>T	p.Pro810Leu	missense_variant	11/11	ENST00000318560.6	NP_005148.2	P00519-1A0A024R8E2Q59FK4
ABL1	NM_007313.3 linkuse as main transcript	c.2486C>T	p.Pro829Leu	missense_variant	11/11		NP_009297.2	P00519-2Q59FK4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABL1	ENST00000318560.6 linkuse as main transcript	c.2429C>T	p.Pro810Leu	missense_variant	11/11	1	NM_005157.6	ENSP00000323315.5		P00519-1
ABL1	ENST00000372348.9 linkuse as main transcript	c.2486C>T	p.Pro829Leu	missense_variant	11/11	1		ENSP00000361423.2		P00519-2

Frequencies

GnomAD3 genomes

AF:

0.00480

AC:

731

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00754

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00538

AC:

1318

AN:

244984

Hom.:

AF XY:

0.00541

AC XY:

725

AN XY:

134024

show subpopulations

Gnomad AFR exome

AF:

0.000805

Gnomad AMR exome

AF:

0.00387

Gnomad ASJ exome

AF:

0.0153

Gnomad EAS exome

AF:

0.0000552

Gnomad SAS exome

AF:

0.00226

Gnomad FIN exome

AF:

0.00336

Gnomad NFE exome

AF:

0.00770

Gnomad OTH exome

AF:

0.00584

GnomAD4 exome

AF:

0.00673

AC:

9833

AN:

1460280

Hom.:

Cov.:

AF XY:

0.00670

AC XY:

4867

AN XY:

726418

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.00392

Gnomad4 ASJ exome

AF:

0.0150

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00259

Gnomad4 FIN exome

AF:

0.00392

Gnomad4 NFE exome

AF:

0.00755

Gnomad4 OTH exome

AF:

0.00603

GnomAD4 genome

AF:

0.00480

AC:

731

AN:

152278

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

343

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00398

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00754

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00696

Hom.:

Bravo

AF:

0.00470

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00930

AC:

ExAC

AF:

0.00541

AC:

656

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00845

EpiControl

AF:

0.00949

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	ABL1: BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

.;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D

MetaRNN

Benign

0.0084

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.5

D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.0030

D;D

Sift4G

Benign

0.17

T;T

Polyphen

1.0

.;D

Vest4

0.50

MVP

0.55

MPC

0.81

ClinPred

0.048

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.19

gMVP

0.16

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