rs2855192

Variant names:

• chr9-130852664-G-A
• rs2855192
• NM_005157.6:c.80-1400G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-130852664-G-A
• chr9-130852664-G-C

Variant summary

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

The NM_007313.3(ABL1):​c.137-1400G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0868 in 151,822 control chromosomes in the GnomAD database, including 759 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 0.087 (759 hom., cov: 31)
• Consequence: ABL1 NM_007313.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007313.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABL1	NM_005157.6	MANE Select	c.80-1400G>A		intron	N/A	NP_005148.2
	ABL1	NM_007313.3		c.137-1400G>A		intron	N/A	NP_009297.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABL1	ENST00000318560.6	TSL:1 MANE Select	c.80-1400G>A		intron	N/A	ENSP00000323315.5
	ABL1	ENST00000372348.9	TSL:1	c.137-1400G>A		intron	N/A	ENSP00000361423.2
	ABL1	ENST00000929254.1		c.80-1403G>A		intron	N/A	ENSP00000599313.1

Frequencies

GnomAD3 genomes AF: 0.0869 AC: 13183 AN: 151704 Hom.: 759 Cov.: 31

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.0973

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0341

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.0868 AC: 13180 AN: 151822 Hom.: 759 Cov.: 31 AF XY: 0.0833 AC XY: 6178 AN XY: 74160

African (AFR) AF: 0.0225 AC: 932 AN: 41420

American (AMR) AF: 0.0971 AC: 1480 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 639 AN: 3464

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0347 AC: 167 AN: 4812

European-Finnish (FIN) AF: 0.0895 AC: 937 AN: 10468

Middle Eastern (MID) AF: 0.169 AC: 49 AN: 290

European-Non Finnish (NFE) AF: 0.128 AC: 8667 AN: 67928

Other (OTH) AF: 0.115 AC: 243 AN: 2110

Alfa AF: 0.0967 Hom.: 729

Bravo AF: 0.0880

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.75
PhyloP100		-0.066
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: rs2855192; hg19: chr9-133728051;