chr4-106324979-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Publications

12 publications found

Variant links:

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

AIMP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1279491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AIMP1	NM_001142416.2	MANE Select	c.-25-6C>A	splice_region intron	N/A	NP_001135888.2	Q12904-1
AIMP1	NM_001142415.2		c.-25-6C>A	splice_region intron	N/A	NP_001135887.1	Q12904-1
AIMP1	NM_004757.4		c.-25-6C>A	splice_region intron	N/A	NP_004748.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AIMP1	ENST00000672341.1	MANE Select	c.-25-6C>A	splice_region intron	N/A	ENSP00000500620.1	Q12904-1
AIMP1	ENST00000394701.6	TSL:1	c.-161-2472C>A	intron	N/A	ENSP00000378191.5	A0A8C8KIA0
AIMP1	ENST00000358008.7	TSL:2	c.-25-6C>A	splice_region intron	N/A	ENSP00000350699.3	Q12904-1

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25465

AN:

151516

Hom.:

2185

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.173

AC:

40414

AN:

233740

AF XY:

0.177

show subpopulations

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 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.:

AF XY:

0.179

AC XY:

127166

AN XY:

711966

show subpopulations

African (AFR)

AF:

0.154

AC:

4991

AN:

32422

American (AMR)

AF:

0.127

AC:

5348

AN:

41980

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

3015

AN:

25330

East Asian (EAS)

AF:

0.175

AC:

6859

AN:

39102

South Asian (SAS)

AF:

0.246

AC:

19688

AN:

79998

European-Finnish (FIN)

AF:

0.200

AC:

10535

AN:

52724

Middle Eastern (MID)

AF:

0.143

AC:

707

AN:

4940

European-Non Finnish (NFE)

AF:

0.175

AC:

191997

AN:

1098370

Other (OTH)

AF:

0.176

AC:

10424

AN:

59092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

8625

17250

25874

34499

43124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6828

13656

20484

27312

34140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.168

AC:

25474

AN:

151634

Hom.:

2184

Cov.:

AF XY:

0.169

AC XY:

12554

AN XY:

74076

show subpopulations

African (AFR)

AF:

0.161

AC:

6645

AN:

41362

American (AMR)

AF:

0.130

AC:

1974

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

427

AN:

3468

East Asian (EAS)

AF:

0.139

AC:

718

AN:

5174

South Asian (SAS)

AF:

0.250

AC:

1202

AN:

4814

European-Finnish (FIN)

AF:

0.200

AC:

2099

AN:

10490

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.174

AC:

11829

AN:

67802

Other (OTH)

AF:

0.151

AC:

316

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1094

2188

3282

4376

5470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.171

Hom.:

8209

Bravo

AF:

0.161

Asia WGS

AF:

0.213

AC:

739

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.9

(source)

DANN

Benign

0.47

PhyloP100

-0.0040

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over