Variant 4-106324979-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001142416.2(AIMP1):c.-25-6C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,585,592 control chromosomes in the GnomAD database, including 25,421 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2184 hom., cov: 32)

Exomes 𝑓: 0.18 ( 23237 hom. )

Consequence

AIMP1
NM_001142416.2 splice_region, intron

Scores

Splicing: ADA: 0.0001557

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.00400

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:

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=-0.57).

BP6

Variant 4-106324979-C-A is Benign according to our data. Variant chr4-106324979-C-A is described in ClinVar as [Benign]. Clinvar id is 1279491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-106324979-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIMP1	NM_001142416.2 link	c.-25-6C>A		splice_region_variant, intron_variant		ENST00000672341.1	NP_001135888.2	Q12904-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIMP1	ENST00000672341.1 link	c.-25-6C>A		splice_region_variant, intron_variant			NM_001142416.2	ENSP00000500620.1		Q12904-1

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25465

AN:

151516

Hom.:

2185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.150

GnomAD3 exomes

AF:

0.173

AC:

40414

AN:

233740

Hom.:

3622

AF XY:

0.177

AC XY:

22452

AN XY:

126578

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.127

Gnomad ASJ exome

AF:

0.119

Gnomad EAS exome

AF:

0.140

Gnomad SAS exome

AF:

0.249

Gnomad FIN exome

AF:

0.197

Gnomad NFE exome

AF:

0.175

Gnomad OTH exome

AF:

0.174

GnomAD4 exome

AF:

0.177

AC:

253564

AN:

1433958

Hom.:

23237

Cov.:

AF XY:

0.179

AC XY:

127166

AN XY:

711966

show subpopulations

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.175

Gnomad4 SAS exome

AF:

0.246

Gnomad4 FIN exome

AF:

0.200

Gnomad4 NFE exome

AF:

0.175

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.168

AC:

25474

AN:

151634

Hom.:

2184

Cov.:

AF XY:

0.169

AC XY:

12554

AN XY:

74076

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.130

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.139

Gnomad4 SAS

AF:

0.250

Gnomad4 FIN

AF:

0.200

Gnomad4 NFE

AF:

0.174

Gnomad4 OTH

AF:

0.151

Alfa

AF:

0.167

Hom.:

3369

Bravo

AF:

0.161

Asia WGS

AF:

0.213

AC:

739

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 24% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 22. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.9

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.052

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