rs11544777

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
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• hypomyelinating leukodystrophy 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142416.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIMP1	NM_001142416.2	MANE Select	c.24G>C	p.Leu8Leu	synonymous	Exon 2 of 7	NP_001135888.2	Q12904-1
	AIMP1	NM_001142415.2		c.24G>C	p.Leu8Leu	synonymous	Exon 2 of 7	NP_001135887.1	Q12904-1
	AIMP1	NM_004757.4		c.24G>C	p.Leu8Leu	synonymous	Exon 2 of 7	NP_004748.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIMP1	ENST00000672341.1	MANE Select	c.24G>C	p.Leu8Leu	synonymous	Exon 2 of 7	ENSP00000500620.1	Q12904-1
	AIMP1	ENST00000394701.6	TSL:1	c.-161-2418G>C		intron	N/A	ENSP00000378191.5	A0A8C8KIA0
	AIMP1	ENST00000358008.7	TSL:2	c.24G>C	p.Leu8Leu	synonymous	Exon 2 of 7	ENSP00000350699.3	Q12904-1

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

African (AFR) AF: 0.00930 AC: 311 AN: 33424

American (AMR) AF: 0.0170 AC: 759 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.0355 AC: 926 AN: 26052

East Asian (EAS) AF: 0.000177 AC: 7 AN: 39576

South Asian (SAS) AF: 0.00579 AC: 497 AN: 85856

European-Finnish (FIN) AF: 0.0871 AC: 4645 AN: 53346

Middle Eastern (MID) AF: 0.0239 AC: 137 AN: 5730

European-Non Finnish (NFE) AF: 0.0644 AC: 71512 AN: 1110502

Other (OTH) 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

African (AFR) AF: 0.0108 AC: 447 AN: 41556

American (AMR) AF: 0.0185 AC: 283 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0338 AC: 117 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00663 AC: 32 AN: 4824

European-Finnish (FIN) AF: 0.0972 AC: 1029 AN: 10586

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0667 AC: 4527 AN: 67904

Other (OTH) AF: 0.0384 AC: 81 AN: 2110

Alfa AF: 0.0577 Hom.: 100

Bravo AF: 0.0359

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.5
DANN	Benign	0.75
PhyloP100		2.5
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

Other links and lift over

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