rs7457

Variant names:

• chr9-130887439-C-T
• rs7457
• NM_005157.6:c.*1756C>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.*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
• Publications: 12 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=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 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.*1756C>T		3_prime_UTR	Exon 11 of 11	NP_005148.2	P00519-1
	ABL1	NM_007313.3		c.*1756C>T		3_prime_UTR	Exon 11 of 11	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.*1756C>T		3_prime_UTR	Exon 11 of 11	ENSP00000323315.5	P00519-1
	ABL1	ENST00000372348.9	TSL:1	c.*1756C>T		3_prime_UTR	Exon 11 of 11	ENSP00000361423.2	P00519-2
	ABL1	ENST00000929254.1		c.*1756C>T		3_prime_UTR	Exon 11 of 11	ENSP00000599313.1

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

African (AFR) AF: 0.246 AC: 956 AN: 3892

American (AMR) AF: 0.0757 AC: 189 AN: 2496

Ashkenazi Jewish (ASJ) AF: 0.0658 AC: 337 AN: 5122

East Asian (EAS) AF: 0.0000878 AC: 1 AN: 11394

South Asian (SAS) AF: 0.0171 AC: 12 AN: 702

European-Finnish (FIN) AF: 0.0284 AC: 8 AN: 282

Middle Eastern (MID) AF: 0.0955 AC: 47 AN: 492

European-Non Finnish (NFE) AF: 0.0790 AC: 3944 AN: 49942

Other (OTH) AF: 0.0917 AC: 620 AN: 6760

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

African (AFR) AF: 0.235 AC: 9734 AN: 41480

American (AMR) AF: 0.0789 AC: 1206 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0628 AC: 218 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.0268 AC: 129 AN: 4816

European-Finnish (FIN) AF: 0.0322 AC: 341 AN: 10600

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0768 AC: 5226 AN: 68012

Other (OTH) AF: 0.0995 AC: 210 AN: 2110

Alfa AF: 0.0929 Hom.: 1127

Bravo AF: 0.121

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.80
PhyloP100		2.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7457; hg19: chr9-133762826;