2-99155218-G-C

Position:

• chr2-99155218-G-C

Variant summary

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

The NM_001204830.2(LIPT1):​c.-278G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 373,784 control chromosomes in the GnomAD database, including 3,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1347 hom., cov: 32)
  • Exomes 𝑓: 0.14 (2381 hom.)
• Consequence: LIPT1 NM_001204830.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.277

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-99155218-G-C is Benign according to our data. Variant chr2-99155218-G-C is described in ClinVar as [Benign]. Clinvar id is 1239663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPT1	NM_145199.3	c.-2+167G>C		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+167G>C		intron_variant			NM_145199.3	ENSP00000498546.1
ENSG00000273155	ENST00000410042.1	c.-154+167G>C		intron_variant		2		ENSP00000387111.1
ENSG00000241962	ENST00000424491.5	n.63+4699G>C		intron_variant		2		ENSP00000390891.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17668 AN: 152088 Hom.: 1348 Cov.: 32

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0810

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.137 AC: 30337 AN: 221578 Hom.: 2381 Cov.: 0 AF XY: 0.132 AC XY: 16321 AN XY: 123390

Gnomad4 AFR exome AF: 0.0311

Gnomad4 AMR exome AF: 0.0810

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.000468

Gnomad4 SAS exome AF: 0.0975

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.148

GnomAD4 genome AF: 0.116 AC: 17658 AN: 152206 Hom.: 1347 Cov.: 32 AF XY: 0.113 AC XY: 8408 AN XY: 74402

Gnomad4 AFR AF: 0.0320

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0806

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.130

Alfa AF: 0.134 Hom.: 206

Bravo AF: 0.110

Asia WGS AF: 0.0400 AC: 141 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 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.4
DANN	Benign	0.64

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: rs17760028; hg19: chr2-99771681;