chr4-106324979-C-A

Variant names:

• chr4-106324979-C-A
• rs3737498
• NM_001142416.2:c.-25-6C>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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

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]

ACMG classification

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 rank	MANE	Protein	UniProt
AIMP1	NM_001142416.2	c.-25-6C>A		splice_region_variant, intron_variant	Intron 1 of 6	ENST00000672341.1	NP_001135888.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIMP1	ENST00000672341.1	c.-25-6C>A		splice_region_variant, intron_variant	Intron 1 of 6		NM_001142416.2	ENSP00000500620.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25465 AN: 151516 Hom.: 2185 Cov.: 32

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

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.: 30 AF XY: 0.179 AC XY: 127166 AN XY: 711966

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.: 32 AF XY: 0.169 AC XY: 12554 AN XY: 74076

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Other links and lift over

dbSNP: rs3737498; hg19: chr4-107246136; COSMIC: COSV56756194; COSMIC: COSV56756194;