9-130858688-C-T

Variant names:

• chr9-130858688-C-T
• rs3824400
• NM_005157.6:c.549+3592C>T

Variant summary

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

The NM_005157.6(ABL1):​c.549+3592C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,070 control chromosomes in the GnomAD database, including 5,336 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 0.22 (5336 hom., cov: 32)
• Consequence: ABL1 NM_005157.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317
• Publications: 10 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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 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.549+3592C>T		intron	N/A	NP_005148.2
	ABL1	NM_007313.3		c.606+3592C>T		intron	N/A	NP_009297.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABL1	ENST00000318560.6	TSL:1 MANE Select	c.549+3592C>T		intron	N/A	ENSP00000323315.5
	ABL1	ENST00000372348.9	TSL:1	c.606+3592C>T		intron	N/A	ENSP00000361423.2
	ABL1	ENST00000929254.1		c.546+3592C>T		intron	N/A	ENSP00000599313.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33870 AN: 151950 Hom.: 5316 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0583

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.223 AC: 33938 AN: 152070 Hom.: 5336 Cov.: 32 AF XY: 0.218 AC XY: 16231 AN XY: 74344

African (AFR) AF: 0.452 AC: 18733 AN: 41426

American (AMR) AF: 0.202 AC: 3093 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3472

East Asian (EAS) AF: 0.0582 AC: 301 AN: 5174

South Asian (SAS) AF: 0.103 AC: 495 AN: 4824

European-Finnish (FIN) AF: 0.117 AC: 1234 AN: 10572

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8966 AN: 67988

Other (OTH) AF: 0.216 AC: 457 AN: 2114

Alfa AF: 0.158 Hom.: 4166

Bravo AF: 0.239

Asia WGS AF: 0.130 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.5
DANN	Benign	0.58
PhyloP100		0.32
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: rs3824400; hg19: chr9-133734075;