4-106325033-G-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001142416.2(AIMP1):c.24G>C(p.Leu8=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 1,611,490 control chromosomes in the GnomAD database, including 2,944 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (222 hom., cov: 32)
  • Exomes 𝑓: 0.056 (2722 hom.)
• Consequence: AIMP1 NM_001142416.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.47

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 4-106325033-G-C is Benign according to our data. Variant chr4-106325033-G-C is described in ClinVar as [Benign]. Clinvar id is 1169308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.065 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AIMP1	NM_001142416.2	c.24G>C	p.Leu8=	synonymous_variant	2/7	ENST00000672341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AIMP1	ENST00000672341.1	c.24G>C	p.Leu8=	synonymous_variant	2/7		NM_001142416.2	P1

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6558 AN: 151992 Hom.: 222 Cov.: 32

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.0185

Gnomad ASJ AF: 0.0338

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.0972

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0667

Gnomad OTH AF: 0.0388

GnomAD3 exomes AF: 0.0413 AC: 10334 AN: 250422 Hom.: 323 AF XY: 0.0414 AC XY: 5603 AN XY: 135386

Gnomad AFR exome AF: 0.0109

Gnomad AMR exome AF: 0.0160

Gnomad ASJ exome AF: 0.0349

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.00496

Gnomad FIN exome AF: 0.0890

Gnomad NFE exome AF: 0.0609

Gnomad OTH exome AF: 0.0453

GnomAD4 exome AF: 0.0559 AC: 81591 AN: 1459380 Hom.: 2722 Cov.: 31 AF XY: 0.0547 AC XY: 39690 AN XY: 725950

Gnomad4 AFR exome AF: 0.00930

Gnomad4 AMR exome AF: 0.0170

Gnomad4 ASJ exome AF: 0.0355

Gnomad4 EAS exome AF: 0.000177

Gnomad4 SAS exome AF: 0.00579

Gnomad4 FIN exome AF: 0.0871

Gnomad4 NFE exome AF: 0.0644

Gnomad4 OTH exome AF: 0.0464

GnomAD4 genome AF: 0.0431 AC: 6558 AN: 152110 Hom.: 222 Cov.: 32 AF XY: 0.0422 AC XY: 3141 AN XY: 74354

Gnomad4 AFR AF: 0.0108

Gnomad4 AMR AF: 0.0185

Gnomad4 ASJ AF: 0.0338

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00663

Gnomad4 FIN AF: 0.0972

Gnomad4 NFE AF: 0.0667

Gnomad4 OTH AF: 0.0384

Alfa AF: 0.0577 Hom.: 100

Bravo AF: 0.0359

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	7.5
Dann	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs11544777; hg19: chr4-107246190; COSMIC: COSV56763584; COSMIC: COSV56763584;