4-106316858-A-G

Position:

• chr4-106316858-A-G

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.-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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.948

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 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
AIMP1	NM_001142416.2	c.-26+264A>G		intron_variant		ENST00000672341.1	NP_001135888.2
AIMP1	NM_001142415.2	c.-26+1222A>G		intron_variant			NP_001135887.1
AIMP1	NM_004757.4	c.-26+514A>G		intron_variant			NP_004748.2
AIMP1	XM_047416410.1	c.-26+48A>G		intron_variant			XP_047272366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIMP1	ENST00000672341.1	c.-26+264A>G		intron_variant			NM_001142416.2	ENSP00000500620.1

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5690 AN: 152174 Hom.: 156 Cov.: 32

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

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.: 32 AF XY: 0.0363 AC XY: 2700 AN XY: 74458

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.: 10

Bravo AF: 0.0355

Asia WGS AF: 0.00606 AC: 21 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

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

Other links and lift over

dbSNP: rs62318117; hg19: chr4-107238015;