1-39883721-G-A

Variant names:

• chr1-39883721-G-A
• rs7543162
• NR_183424.1:n.272+300G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NR_183424.1(MYCL-AS1):​n.272+300G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 151,852 control chromosomes in the GnomAD database, including 754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.063 (754 hom., cov: 31)
• Consequence: MYCL-AS1 NR_183424.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.670

Genes affected

MYCL-AS1 (HGNC:40386): (MYCL antisense RNA 1)

TRIT1 (HGNC:20286): (tRNA isopentenyltransferase 1) This gene encodes a protein that that is targeted to the mitochondrion and modifies transfer RNAs (tRNAs) by adding a dimethylallyl group onto the adenine at position 37. This modification is important for maintaining the correct reading frame during protein translation. This gene is considered a tumor suppressor and its expression can decrease cell growth. Alternative splicing results in multiple transcripts variants, most of which are likely non-functional. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-39883721-G-A is Benign according to our data. Variant chr1-39883721-G-A is described in ClinVar as [Benign]. Clinvar id is 1281052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIT1	NM_017646.6	c.-230C>T		upstream_gene_variant		ENST00000316891.10	NP_060116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIT1	ENST00000316891.10	c.-230C>T		upstream_gene_variant		1	NM_017646.6	ENSP00000321810.5
TRIT1	ENST00000372818.5	c.-230C>T		upstream_gene_variant		1		ENSP00000361905.1
TRIT1	ENST00000462797.5	n.-230C>T		upstream_gene_variant		5		ENSP00000473773.1
TRIT1	ENST00000486825.6	n.-248C>T		upstream_gene_variant		5		ENSP00000474151.1
TRIT1	ENST00000489945.5	n.-230C>T		upstream_gene_variant		5		ENSP00000473745.1
TRIT1	ENST00000492612.6	n.-242C>T		upstream_gene_variant		5		ENSP00000473708.1

Frequencies

GnomAD3 genomes AF: 0.0630 AC: 9562 AN: 151734 Hom.: 753 Cov.: 31

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0335

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.0264

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00277

Gnomad OTH AF: 0.0465

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0631 AC: 9582 AN: 151852 Hom.: 754 Cov.: 31 AF XY: 0.0632 AC XY: 4690 AN XY: 74206

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.0336

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.0254

Gnomad4 FIN AF: 0.0303

Gnomad4 NFE AF: 0.00275

Gnomad4 OTH AF: 0.0479

Alfa AF: 0.0430 Hom.: 55

Bravo AF: 0.0707

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 28, 2018

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	-0.80
CADD	Benign	6.3
DANN	Benign	0.93

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7543162; hg19: chr1-40349393;