10-26750588-T-G

Variant names:

• chr10-26750588-T-G
• rs2368184
• NM_001012750.3:c.1270+1010A>C

Variant summary

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

The NM_001012750.3(ABI1):​c.1270+1010A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,072 control chromosomes in the GnomAD database, including 27,655 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 0.58 (27655 hom., cov: 33)
• Consequence: ABI1 NM_001012750.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 2 publications found

Genes affected

ABI1 (HGNC:11320): (abl interactor 1) This gene encodes a member of the Abelson-interactor family of adaptor proteins. These proteins facilitate signal transduction as components of several multiprotein complexes, and regulate actin polymerization and cytoskeletal remodeling through interactions with Abelson tyrosine kinases. The encoded protein plays a role in macropinocytosis as a component of the WAVE2 complex, and also forms a complex with EPS8 and SOS1 that mediates signal transduction from Ras to Rac. This gene may play a role in the progression of several malignancies including melanoma, colon cancer and breast cancer, and a t(10;11) chromosomal translocation involving this gene and the MLL gene has been associated with acute myeloid leukemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 14. [provided by RefSeq, Sep 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012750.3. 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
	ABI1	NM_001012750.3	MANE Select	c.1270+1010A>C		intron	N/A	NP_001012768.1	Q8IZP0-9
	ABI1	NM_005470.4		c.1351+1010A>C		intron	N/A	NP_005461.2	Q8IZP0-1
	ABI1	NM_001348029.2		c.1348+1010A>C		intron	N/A	NP_001334958.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABI1	ENST00000376140.4	TSL:5 MANE Select	c.1270+1010A>C		intron	N/A	ENSP00000365310.3	Q8IZP0-9
	ABI1	ENST00000376142.6	TSL:1	c.1351+1010A>C		intron	N/A	ENSP00000365312.2	Q8IZP0-1
	ABI1	ENST00000359188.8	TSL:1	c.1267+1010A>C		intron	N/A	ENSP00000352114.4	Q8IZP0-6

Frequencies

GnomAD3 genomes AF: 0.579 AC: 88037 AN: 151954 Hom.: 27580 Cov.: 33

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.580 AC: 88179 AN: 152072 Hom.: 27655 Cov.: 33 AF XY: 0.583 AC XY: 43357 AN XY: 74322

African (AFR) AF: 0.832 AC: 34524 AN: 41500

American (AMR) AF: 0.557 AC: 8512 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1913 AN: 3470

East Asian (EAS) AF: 0.650 AC: 3361 AN: 5174

South Asian (SAS) AF: 0.600 AC: 2892 AN: 4820

European-Finnish (FIN) AF: 0.492 AC: 5191 AN: 10542

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.440 AC: 29908 AN: 67962

Other (OTH) AF: 0.571 AC: 1204 AN: 2108

Alfa AF: 0.427 Hom.: 2548

Bravo AF: 0.594

Asia WGS AF: 0.643 AC: 2237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.6
DANN	Benign	0.69
PhyloP100		-0.13
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: rs2368184; hg19: chr10-27039517;