chr9-130882398-G-A

Variant names:

• chr9-130882398-G-A
• rs3808814
• NM_005157.6:c.1679-1571G>A

Variant summary

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

The NM_005157.6(ABL1):​c.1679-1571G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,096 control chromosomes in the GnomAD database, including 1,236 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 0.12 (1236 hom., cov: 32)
• Consequence: ABL1 NM_005157.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 7 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: G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005157.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABL1	NM_005157.6	MANE Select	c.1679-1571G>A		intron	N/A	NP_005148.2	P00519-1
	ABL1	NM_007313.3		c.1736-1571G>A		intron	N/A	NP_009297.2	P00519-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABL1	ENST00000318560.6	TSL:1 MANE Select	c.1679-1571G>A		intron	N/A	ENSP00000323315.5	P00519-1
	ABL1	ENST00000372348.9	TSL:1	c.1736-1571G>A		intron	N/A	ENSP00000361423.2	P00519-2
	ABL1	ENST00000929254.1		c.1676-1571G>A		intron	N/A	ENSP00000599313.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18048 AN: 151978 Hom.: 1232 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.0605

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0919

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0913

Gnomad OTH AF: 0.0909

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

GnomAD4 genome AF: 0.119 AC: 18089 AN: 152096 Hom.: 1236 Cov.: 32 AF XY: 0.121 AC XY: 8966 AN XY: 74346

African (AFR) AF: 0.186 AC: 7692 AN: 41444

American (AMR) AF: 0.123 AC: 1884 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0660 AC: 229 AN: 3470

East Asian (EAS) AF: 0.0602 AC: 312 AN: 5180

South Asian (SAS) AF: 0.110 AC: 530 AN: 4826

European-Finnish (FIN) AF: 0.0919 AC: 973 AN: 10590

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0913 AC: 6207 AN: 67986

Other (OTH) AF: 0.0919 AC: 194 AN: 2112

Alfa AF: 0.0894 Hom.: 1130

Bravo AF: 0.122

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.066
DANN	Benign	0.59
PhyloP100		-1.3
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: rs3808814; hg19: chr9-133757785;