dbSNP rs62318117: AIMP1:c.-26+264A>G (chr4-106316858-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001142416.2(AIMP1):c.-26+264A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0413 in 442,586 control chromosomes in the GnomAD database, including 495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 156 hom., cov: 32)

Exomes 𝑓: 0.043 ( 339 hom. )

Consequence

AIMP1
NM_001142416.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.948

Variant links:

Genes affected

AIMP1 (HGNC:10648): (aminoacyl tRNA synthetase complex interacting multifunctional protein 1) The protein encoded by this gene is a cytokine that is specifically induced by apoptosis, and it is involved in the control of angiogenesis, inflammation, and wound healing. The release of this cytokine renders the tumor-associated vasculature sensitive to tumor necrosis factor. The precursor protein is identical to the p43 subunit, which is associated with the multi-tRNA synthetase complex, and it modulates aminoacylation activity of tRNA synthetase in normal cells. This protein is also involved in the stimulation of inflammatory responses after proteolytic cleavage in tumor cells. Multiple transcript variants encoding different isoforms have been found for this gene. A pseudogene has been identified on chromosome 20. [provided by RefSeq, Dec 2008]

AIMP1 links:

TBCK (HGNC:28261): (TBC1 domain containing kinase) This gene encodes a protein that contains a protein kinase domain, a Rhodanase-like domain and the Tre-2/Bub2/Cdc16 (TBC) domain. The encoded protein is thought to play a role in actin organization, cell growth and cell proliferation by regulating the mammalian target of the rapamycin (mTOR) signaling pathway. This protein may also be involved in the transcriptional regulation of the components of the mTOR complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

TBCK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 4-106316858-A-G is Benign according to our data. Variant chr4-106316858-A-G is described in ClinVar as [Benign]. Clinvar id is 1283130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIMP1	NM_001142416.2 link	c.-26+264A>G		intron_variant	Intron 1 of 6	ENST00000672341.1	NP_001135888.2	Q12904-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIMP1	ENST00000672341.1 link	c.-26+264A>G		intron_variant	Intron 1 of 6		NM_001142416.2	ENSP00000500620.1		Q12904-1

Frequencies

GnomAD3 genomes

AF:

0.0374

AC:

5690

AN:

152174

Hom.:

156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00989

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0432

Gnomad ASJ

AF:

0.0616

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00787

Gnomad FIN

AF:

0.0361

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0558

Gnomad OTH

AF:

0.0387

GnomAD4 exome

AF:

0.0434

AC:

12592

AN:

290294

Hom.:

339

AF XY:

0.0426

AC XY:

6381

AN XY:

149670

show subpopulations

Gnomad4 AFR exome

AF:

0.00920

Gnomad4 AMR exome

AF:

0.0333

Gnomad4 ASJ exome

AF:

0.0629

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0111

Gnomad4 FIN exome

AF:

0.0346

Gnomad4 NFE exome

AF:

0.0555

Gnomad4 OTH exome

AF:

0.0403

GnomAD4 genome

AF:

0.0373

AC:

5686

AN:

152292

Hom.:

156

Cov.:

AF XY:

0.0363

AC XY:

2700

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00986

Gnomad4 AMR

AF:

0.0431

Gnomad4 ASJ

AF:

0.0616

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00767

Gnomad4 FIN

AF:

0.0361

Gnomad4 NFE

AF:

0.0558

Gnomad4 OTH

AF:

0.0383

Alfa

AF:

0.0131

Hom.:

Bravo

AF:

0.0355

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.6

DANN

Benign

0.51

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

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