chr10-26765220-G-C

Position:

chr10-26765220-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001012750.3(ABI1):c.818C>G(p.Pro273Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000042 in 1,595,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

ABI1
NM_001012750.3 missense, splice_region

Scores

Splicing: ADA: 0.9596

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.17

Variant links:

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]

ABI1 links:

ABI1 (HGNC:):

ABI1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20720777).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABI1	NM_001012750.3 linkuse as main transcript	c.818C>G	p.Pro273Arg	missense_variant, splice_region_variant	7/11	ENST00000376140.4	NP_001012768.1	Q8IZP0-9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABI1	ENST00000376140.4 linkuse as main transcript	c.818C>G	p.Pro273Arg	missense_variant, splice_region_variant	7/11	5	NM_001012750.3	ENSP00000365310.3		Q8IZP0-9

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000256

AC:

AN:

234360

Hom.:

AF XY:

0.0000159

AC XY:

AN XY:

126054

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000416

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000938

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

AF:

0.0000422

AC:

AN:

1443798

Hom.:

Cov.:

AF XY:

0.0000307

AC XY:

AN XY:

717442

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000236

Gnomad4 ASJ exome

AF:

0.000739

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000317

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151908

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74166

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000901

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2024

The c.818C>G (p.P273R) alteration is located in exon 7 (coding exon 7) of the ABI1 gene. This alteration results from a C to G substitution at nucleotide position 818, causing the proline (P) at amino acid position 273 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

.;T;.;.;T;.;.;.;.;.;.;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.82

T;D;T;T;T;T;D;T;D;D;D;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.21

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

2.0

M;M;M;.;.;.;M;.;.;M;.;M

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-5.3

D;D;D;D;D;D;D;D;.;.;D;D

REVEL

Benign

0.083

Sift

Uncertain

0.0010

D;D;D;D;D;D;D;D;.;.;D;D

Sift4G

Uncertain

0.0080

D;T;D;D;D;D;D;D;D;T;T;D

Polyphen

0.097, 0.55, 0.076, 0.012, 0.70

.;B;P;B;.;.;P;.;B;.;.;P

Vest4

0.49

MutPred

0.27

Gain of solvent accessibility (P = 0.0202);Gain of solvent accessibility (P = 0.0202);Gain of solvent accessibility (P = 0.0202);.;.;.;Gain of solvent accessibility (P = 0.0202);.;Gain of solvent accessibility (P = 0.0202);Gain of solvent accessibility (P = 0.0202);.;Gain of solvent accessibility (P = 0.0202);

MVP

0.45

MPC

0.56

ClinPred

0.26

GERP RS

5.7

Varity_R

0.25

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.96

dbscSNV1_RF

Benign

0.65

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over