4-106325033-G-C

Variant names:

• chr4-106325033-G-C
• rs11544777
• NM_001142416.2:c.24G>C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001142416.2(AIMP1):​c.24G>C​(p.Leu8Leu) 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:3
• 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AIMP1	NM_001142416.2	c.24G>C	p.Leu8Leu	synonymous_variant	Exon 2 of 7	ENST00000672341.1	NP_001135888.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIMP1	ENST00000672341.1	c.24G>C	p.Leu8Leu	synonymous_variant	Exon 2 of 7		NM_001142416.2	ENSP00000500620.1

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

GnomAD2 exomes AF: 0.0413 AC: 10334 AN: 250422 AF XY: 0.0414

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 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 AC: 311 AN: 33424

Gnomad4 AMR exome AF: 0.0170 AC: 759 AN: 44644

Gnomad4 ASJ exome AF: 0.0355 AC: 926 AN: 26052

Gnomad4 EAS exome AF: 0.000177 AC: 7 AN: 39576

Gnomad4 SAS exome AF: 0.00579 AC: 497 AN: 85856

Gnomad4 FIN exome AF: 0.0871 AC: 4645 AN: 53346

Gnomad4 NFE exome AF: 0.0644 AC: 71512 AN: 1110502

Gnomad4 Remaining exome AF: 0.0464 AC: 2797 AN: 60250

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 AC: 0.0107566 AN: 0.0107566

Gnomad4 AMR AF: 0.0185 AC: 0.0185234 AN: 0.0185234

Gnomad4 ASJ AF: 0.0338 AC: 0.0337565 AN: 0.0337565

Gnomad4 EAS AF: 0.000193 AC: 0.000192901 AN: 0.000192901

Gnomad4 SAS AF: 0.00663 AC: 0.0066335 AN: 0.0066335

Gnomad4 FIN AF: 0.0972 AC: 0.0972039 AN: 0.0972039

Gnomad4 NFE AF: 0.0667 AC: 0.0666676 AN: 0.0666676

Gnomad4 OTH AF: 0.0384 AC: 0.0383886 AN: 0.0383886

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 09, 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	-0.46
CADD	Benign	7.5
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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;