rs12779919

Variant names:

• chr10-26780561-C-T
• rs12779919
• NM_001012750.3:c.286-3320G>A

Variant summary

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

The NM_001012750.3(ABI1):​c.286-3320G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,112 control chromosomes in the GnomAD database, including 2,579 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 0.18 (2579 hom., cov: 32)
• Consequence: ABI1 NM_001012750.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 0 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=-0.69).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABI1	NM_001012750.3	c.286-3320G>A		intron_variant	Intron 2 of 10	ENST00000376140.4	NP_001012768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABI1	ENST00000376140.4	c.286-3320G>A		intron_variant	Intron 2 of 10	5	NM_001012750.3	ENSP00000365310.3

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27113 AN: 151994 Hom.: 2572 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0783

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.178 AC: 27149 AN: 152112 Hom.: 2579 Cov.: 32 AF XY: 0.177 AC XY: 13147 AN XY: 74360

African (AFR) AF: 0.164 AC: 6820 AN: 41496

American (AMR) AF: 0.224 AC: 3426 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 924 AN: 3470

East Asian (EAS) AF: 0.104 AC: 540 AN: 5174

South Asian (SAS) AF: 0.0784 AC: 378 AN: 4822

European-Finnish (FIN) AF: 0.189 AC: 1997 AN: 10586

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12332 AN: 67974

Other (OTH) AF: 0.179 AC: 378 AN: 2110

Alfa AF: 0.186 Hom.: 356

Bravo AF: 0.182

Asia WGS AF: 0.0950 AC: 334 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.6
DANN	Benign	0.55
PhyloP100		1.4
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: rs12779919; hg19: chr10-27069490;