rs2070997

Variant names:

• chr9-130872696-A-G
• rs2070997
• NM_005157.6:c.908-164A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005157.6(ABL1):​c.908-164A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,234 control chromosomes in the GnomAD database, including 1,416 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 0.13 (1416 hom., cov: 33)
• Consequence: ABL1 NM_005157.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 8 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABL1	NM_005157.6	c.908-164A>G		intron_variant	Intron 5 of 10	ENST00000318560.6	NP_005148.2
ABL1	NM_007313.3	c.965-164A>G		intron_variant	Intron 5 of 10		NP_009297.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABL1	ENST00000318560.6	c.908-164A>G		intron_variant	Intron 5 of 10	1	NM_005157.6	ENSP00000323315.5
ABL1	ENST00000372348.9	c.965-164A>G		intron_variant	Intron 5 of 10	1		ENSP00000361423.2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19651 AN: 152116 Hom.: 1413 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0948

Gnomad EAS AF: 0.0620

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.0709

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.126

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.129 AC: 19677 AN: 152234 Hom.: 1416 Cov.: 33 AF XY: 0.126 AC XY: 9351 AN XY: 74438

African (AFR) AF: 0.177 AC: 7341 AN: 41512

American (AMR) AF: 0.150 AC: 2300 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0948 AC: 329 AN: 3472

East Asian (EAS) AF: 0.0621 AC: 322 AN: 5182

South Asian (SAS) AF: 0.0940 AC: 453 AN: 4820

European-Finnish (FIN) AF: 0.0709 AC: 752 AN: 10612

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7822 AN: 68022

Other (OTH) AF: 0.128 AC: 270 AN: 2116

Alfa AF: 0.125 Hom.: 2250

Bravo AF: 0.137

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0030
DANN	Benign	0.33
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2070997; hg19: chr9-133748083;