rs3808815

Variant names:

• chr9-130882308-G-A
• rs3808815
• NM_005157.6:c.1678+1644G>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.1678+1644G>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 152,144 control chromosomes in the GnomAD database, including 1,237 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 (1237 hom., cov: 32)
• Consequence: ABL1 NM_005157.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABL1	NM_005157.6	c.1678+1644G>A		intron_variant	Intron 10 of 10	ENST00000318560.6	NP_005148.2
ABL1	NM_007313.3	c.1735+1644G>A		intron_variant	Intron 10 of 10		NP_009297.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABL1	ENST00000318560.6	c.1678+1644G>A		intron_variant	Intron 10 of 10	1	NM_005157.6	ENSP00000323315.5
ABL1	ENST00000372348.9	c.1735+1644G>A		intron_variant	Intron 10 of 10	1		ENSP00000361423.2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18070 AN: 152026 Hom.: 1233 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.0608

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0918

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0912

Gnomad OTH AF: 0.0904

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

GnomAD4 genome AF: 0.119 AC: 18111 AN: 152144 Hom.: 1237 Cov.: 32 AF XY: 0.121 AC XY: 8981 AN XY: 74370

African (AFR) AF: 0.186 AC: 7716 AN: 41486

American (AMR) AF: 0.123 AC: 1883 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0660 AC: 229 AN: 3468

East Asian (EAS) AF: 0.0605 AC: 313 AN: 5172

South Asian (SAS) AF: 0.111 AC: 533 AN: 4822

European-Finnish (FIN) AF: 0.0918 AC: 973 AN: 10596

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

European-Non Finnish (NFE) AF: 0.0912 AC: 6203 AN: 67996

Other (OTH) AF: 0.0914 AC: 193 AN: 2112

Alfa AF: 0.111 Hom.: 152

Bravo AF: 0.122

Asia WGS AF: 0.107 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.37
PhyloP100		-0.12
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: rs3808815; hg19: chr9-133757695;