rs377450717

chr9-130884784-C-Achr9-130884784-C-Gchr9-130884784-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2 BP4_Moderate BP6_Moderate BS2

The NM_005157.6(ABL1):c.2494C>A(p.His832Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,610,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: ABL1 NM_005157.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 1.85

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• PP2: Missense variant where missense usually causes diseases, ABL1
• BP4: Computational evidence support a benign effect (MetaRNN=0.071394086).
• BP6: Variant 9-130884784-C-A is Benign according to our data. Variant chr9-130884784-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 133441.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABL1	NM_005157.6	c.2494C>A	p.His832Asn	missense_variant	11/11	ENST00000318560.6
ABL1	NM_007313.3	c.2551C>A	p.His851Asn	missense_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABL1	ENST00000318560.6	c.2494C>A	p.His832Asn	missense_variant	11/11	1	NM_005157.6
ABL1	ENST00000372348.9	c.2551C>A	p.His851Asn	missense_variant	11/11	1		P1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000143 AC: 35 AN: 244766 Hom.: 0 AF XY: 0.000112 AC XY: 15 AN XY: 133742

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000555

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000658

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000820

Gnomad OTH exome AF: 0.000838

GnomAD4 exome AF: 0.000149 AC: 217 AN: 1458422 Hom.: 0 Cov.: 32 AF XY: 0.000150 AC XY: 109 AN XY: 725168

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000517

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0000192

Gnomad4 NFE exome AF: 0.000158

Gnomad4 OTH exome AF: 0.000149

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152208 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74344

Gnomad4 AFR AF: 0.0000965

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000212

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000115 AC: 14

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 29, 2023

- -

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	0.070
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.073
Dann	Benign	0.56
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.61	D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.030	N;N
REVEL	Benign	0.095
Sift	Benign	0.18	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.10	.;B
Vest4		0.26
MVP		0.27
MPC		0.25
ClinPred		0.027	T
GERP RS		2.7
Varity_R		0.023
gMVP		0.059

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

Other links and lift over

dbSNP: rs377450717; hg19: chr9-133760171;