1-39883756-G-A

Variant names:

• chr1-39883756-G-A
• rs61781270
• NR_183424.1:n.272+335G>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+335G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 151,176 control chromosomes in the GnomAD database, including 2,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.19 (2792 hom., cov: 32)
• Consequence: MYCL-AS1 NR_183424.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.277

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=-0.75).
• BP6: Variant 1-39883756-G-A is Benign according to our data. Variant chr1-39883756-G-A is described in ClinVar as [Benign]. Clinvar id is 1289286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYCL-AS1	NR_183424.1	n.272+335G>A		intron_variant	Intron 1 of 2
MYCL-AS1	NR_183425.1	n.35+572G>A		intron_variant	Intron 1 of 2
TRIT1	NM_001312691.1	c.-265C>T		upstream_gene_variant			NP_001299620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIT1	ENST00000372818.5	c.-265C>T		upstream_gene_variant		1		ENSP00000361905.1
TRIT1	ENST00000495175.6	n.-265C>T		upstream_gene_variant		1		ENSP00000474264.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28330 AN: 151058 Hom.: 2791 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.00987

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.187 AC: 28331 AN: 151176 Hom.: 2792 Cov.: 32 AF XY: 0.182 AC XY: 13422 AN XY: 73810

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.00989

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.160

Alfa AF: 0.0923 Hom.: 135

Bravo AF: 0.183

Asia WGS AF: 0.111 AC: 388 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 14, 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	-0.75
CADD	Benign	11
DANN	Uncertain	0.97

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs61781270; hg19: chr1-40349428;