4-106316331-C-T

Position:

• chr4-106316331-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_004757.4(AIMP1):​c.-39C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00987 in 559,152 control chromosomes in the GnomAD database, including 233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (176 hom., cov: 31)
  • Exomes 𝑓: 0.0036 (57 hom.)
• Consequence: AIMP1 NM_004757.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0280

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]

TBCK (HGNC:28261): (TBC1 domain containing kinase) This gene encodes a protein that contains a protein kinase domain, a Rhodanase-like domain and the Tre-2/Bub2/Cdc16 (TBC) domain. The encoded protein is thought to play a role in actin organization, cell growth and cell proliferation by regulating the mammalian target of the rapamycin (mTOR) signaling pathway. This protein may also be involved in the transcriptional regulation of the components of the mTOR complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 4-106316331-C-T is Benign according to our data. Variant chr4-106316331-C-T is described in ClinVar as [Benign]. Clinvar id is 1243501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIMP1	NM_004757.4	c.-39C>T		5_prime_UTR_variant	1/7		NP_004748.2
TBCK	NM_001163436.4	c.-30+217G>A		intron_variant			NP_001156908.2
AIMP1	NM_001142415.2	c.-26+695C>T		intron_variant			NP_001135887.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIMP1	ENST00000358008	c.-39C>T		5_prime_UTR_variant	1/7	2		ENSP00000350699.3
TBCK	ENST00000273980.10	c.-30+217G>A		intron_variant		5		ENSP00000273980.4
AIMP1	ENST00000510207.5	c.-26+695C>T		intron_variant		4		ENSP00000423681.1

Frequencies

GnomAD3 genomes AF: 0.0268 AC: 4033 AN: 150490 Hom.: 172 Cov.: 31

Gnomad AFR AF: 0.0937

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000633

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.0221

GnomAD4 exome AF: 0.00359 AC: 1467 AN: 408550 Hom.: 57 Cov.: 4 AF XY: 0.00279 AC XY: 600 AN XY: 215400

Gnomad4 AFR exome AF: 0.0898

Gnomad4 AMR exome AF: 0.00729

Gnomad4 ASJ exome AF: 0.0000789

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000359

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000960

Gnomad4 OTH exome AF: 0.00806

GnomAD4 genome AF: 0.0269 AC: 4051 AN: 150602 Hom.: 176 Cov.: 31 AF XY: 0.0262 AC XY: 1921 AN XY: 73432

Gnomad4 AFR AF: 0.0939

Gnomad4 AMR AF: 0.0100

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000634

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000133

Gnomad4 OTH AF: 0.0219

Alfa AF: 0.00443 Hom.: 6

Bravo AF: 0.0301

Asia WGS AF: 0.00260 AC: 10 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 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.9
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.34		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs72878559; hg19: chr4-107237488;