chr1-179110055-T-C

Variant names:

• chr1-179110055-T-C
• rs3818433
• NM_007314.4:c.1825+227A>G

Variant summary

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

The NM_007314.4(ABL2):​c.1825+227A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,200 control chromosomes in the GnomAD database, including 47,464 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 0.78 (47464 hom., cov: 33)
• Consequence: ABL2 NM_007314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455
• Publications: 7 publications found

Genes affected

ABL2 (HGNC:77): (ABL proto-oncogene 2, non-receptor tyrosine kinase) This gene encodes a member of the Abelson family of nonreceptor tyrosine protein kinases. The protein is highly similar to the c-abl oncogene 1 protein, including the tyrosine kinase, SH2 and SH3 domains, and it plays a role in cytoskeletal rearrangements through its C-terminal F-actin- and microtubule-binding sequences. This gene is expressed in both normal and tumor cells, and is involved in translocation with the ets variant 6 gene in leukemia. Multiple alternatively spliced transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Nov 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007314.4. 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
	ABL2	NM_007314.4	MANE Select	c.1825+227A>G		intron	N/A	NP_009298.1
	ABL2	NM_005158.5		c.1780+227A>G		intron	N/A	NP_005149.4
	ABL2	NM_001168236.2		c.1762+227A>G		intron	N/A	NP_001161708.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABL2	ENST00000502732.6	TSL:1 MANE Select	c.1825+227A>G		intron	N/A	ENSP00000427562.1
	ABL2	ENST00000512653.5	TSL:1	c.1780+227A>G		intron	N/A	ENSP00000423578.1
	ABL2	ENST00000367623.8	TSL:1	c.1762+227A>G		intron	N/A	ENSP00000356595.4

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118820 AN: 152082 Hom.: 47405 Cov.: 33

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.781 AC: 118933 AN: 152200 Hom.: 47464 Cov.: 33 AF XY: 0.782 AC XY: 58196 AN XY: 74412

African (AFR) AF: 0.949 AC: 39420 AN: 41556

American (AMR) AF: 0.691 AC: 10562 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2760 AN: 3470

East Asian (EAS) AF: 0.601 AC: 3104 AN: 5168

South Asian (SAS) AF: 0.700 AC: 3374 AN: 4822

European-Finnish (FIN) AF: 0.807 AC: 8531 AN: 10576

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48845 AN: 68000

Other (OTH) AF: 0.766 AC: 1614 AN: 2108

Alfa AF: 0.718 Hom.: 18943

Bravo AF: 0.777

Asia WGS AF: 0.697 AC: 2424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.36
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3818433; hg19: chr1-179079190;