rs2018904

chr10-26792973-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012750.3(ABI1):c.286-15732A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,078 control chromosomes in the GnomAD database, including 2,578 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 (2578 hom., cov: 32)
• Consequence: ABI1 NM_001012750.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABI1	NM_001012750.3	c.286-15732A>G		intron_variant		ENST00000376140.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABI1	ENST00000376140.4	c.286-15732A>G		intron_variant		5	NM_001012750.3

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27145 AN: 151960 Hom.: 2571 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0781

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.179 AC: 27181 AN: 152078 Hom.: 2578 Cov.: 32 AF XY: 0.177 AC XY: 13149 AN XY: 74318

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0782

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.180

Alfa AF: 0.176 Hom.: 1160

Bravo AF: 0.182

Asia WGS AF: 0.0940 AC: 331 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.2
Dann	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs2018904; hg19: chr10-27081902;