2-99156969-A-G

Position:

• chr2-99156969-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145199.3(LIPT1):​c.-2+1918A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,284 control chromosomes in the GnomAD database, including 1,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1508 hom., cov: 33)
• Consequence: LIPT1 NM_145199.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.658

Genes affected

LIPT1 (HGNC:29569): (lipoyltransferase 1) The process of transferring lipoic acid to proteins is a two-step process. The first step is the activation of lipoic acid by lipoate-activating enzyme to form lipoyl-AMP. For the second step, the protein encoded by this gene transfers the lipoyl moiety to apoproteins. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 13. Read-through transcription also exists between this gene and the neighboring downstream mitochondrial ribosomal protein L30 (MRPL30) gene. [provided by RefSeq, Mar 2011]

ENSG00000273155 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-99156969-A-G is Benign according to our data. Variant chr2-99156969-A-G is described in ClinVar as [Benign]. Clinvar id is 1229716.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPT1	NM_145199.3	c.-2+1918A>G		intron_variant		ENST00000651691.1	NP_660200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPT1	ENST00000651691.1	c.-2+1918A>G		intron_variant			NM_145199.3	ENSP00000498546.1
ENSG00000273155	ENST00000410042.1	c.-28+543A>G		intron_variant		2		ENSP00000387111.1
ENSG00000241962	ENST00000424491.5	n.63+6450A>G		intron_variant		2		ENSP00000390891.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18072 AN: 152166 Hom.: 1508 Cov.: 33

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0876

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0385

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.119 AC: 18068 AN: 152284 Hom.: 1508 Cov.: 33 AF XY: 0.116 AC XY: 8645 AN XY: 74452

Gnomad4 AFR AF: 0.0312

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0876

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0389

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.123

Alfa AF: 0.139 Hom.: 217

Bravo AF: 0.111

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs62156398; hg19: chr2-99773432;