chr9-130887439-C-T

Position:

• chr9-130887439-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005157.6(ABL1):​c.*1756C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0997 in 233,244 control chromosomes in the GnomAD database, including 1,814 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 0.11 (1449 hom., cov: 33)
  • Exomes 𝑓: 0.075 (365 hom.)
• Consequence: ABL1 NM_005157.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.92

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABL1	NM_005157.6	c.*1756C>T		3_prime_UTR_variant	11/11	ENST00000318560.6	NP_005148.2
ABL1	NM_007313.3	c.*1756C>T		3_prime_UTR_variant	11/11		NP_009297.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABL1	ENST00000318560.6	c.*1756C>T		3_prime_UTR_variant	11/11	1	NM_005157.6	ENSP00000323315.5
ABL1	ENST00000372348.9	c.*1756C>T		3_prime_UTR_variant	11/11	1		ENSP00000361423.2

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17125 AN: 152044 Hom.: 1446 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0791

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0268

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0768

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0754 AC: 6114 AN: 81082 Hom.: 365 Cov.: 0 AF XY: 0.0739 AC XY: 2756 AN XY: 37296

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.0757

Gnomad4 ASJ exome AF: 0.0658

Gnomad4 EAS exome AF: 0.0000878

Gnomad4 SAS exome AF: 0.0171

Gnomad4 FIN exome AF: 0.0284

Gnomad4 NFE exome AF: 0.0790

Gnomad4 OTH exome AF: 0.0917

GnomAD4 genome AF: 0.113 AC: 17145 AN: 152162 Hom.: 1449 Cov.: 33 AF XY: 0.106 AC XY: 7921 AN XY: 74396

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.0789

Gnomad4 ASJ AF: 0.0628

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0268

Gnomad4 FIN AF: 0.0322

Gnomad4 NFE AF: 0.0768

Gnomad4 OTH AF: 0.0995

Alfa AF: 0.0880 Hom.: 742

Bravo AF: 0.121

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7457; hg19: chr9-133762826;