11-74491959-G-A

Position:

• chr11-74491959-G-A

Variant summary

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

The NM_001144869.3(LIPT2):​c.*176C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 592,680 control chromosomes in the GnomAD database, including 104,625 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23586 hom., cov: 31)
  • Exomes 𝑓: 0.60 (81039 hom.)
• Consequence: LIPT2 NM_001144869.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.800

Genes affected

LIPT2 (HGNC:37216): (lipoyl(octanoyl) transferase 2) This gene encodes a mitochondrial protein that catalyzes the transfer of octanoic acid to lipoate-dependent enzymes such as octanoyl-ACP. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-74491959-G-A is Benign according to our data. Variant chr11-74491959-G-A is described in ClinVar as [Benign]. Clinvar id is 1277061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPT2	NM_001144869.3	c.*176C>T		3_prime_UTR_variant	2/2	ENST00000310109.5
LIPT2	NM_001329941.2	c.*286C>T		3_prime_UTR_variant	2/2
LIPT2	NM_001329942.2	c.*286C>T		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPT2	ENST00000310109.5	c.*176C>T		3_prime_UTR_variant	2/2	2	NM_001144869.3	P1
LIPT2	ENST00000527115.1	c.*286C>T		3_prime_UTR_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83306 AN: 151676 Hom.: 23596 Cov.: 31

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.548

GnomAD4 exome AF: 0.602 AC: 265319 AN: 440886 Hom.: 81039 Cov.: 3 AF XY: 0.598 AC XY: 138096 AN XY: 231052

Gnomad4 AFR exome AF: 0.401

Gnomad4 AMR exome AF: 0.512

Gnomad4 ASJ exome AF: 0.619

Gnomad4 EAS exome AF: 0.677

Gnomad4 SAS exome AF: 0.494

Gnomad4 FIN exome AF: 0.588

Gnomad4 NFE exome AF: 0.629

Gnomad4 OTH exome AF: 0.594

GnomAD4 genome AF: 0.549 AC: 83322 AN: 151794 Hom.: 23586 Cov.: 31 AF XY: 0.543 AC XY: 40271 AN XY: 74140

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.545

Alfa AF: 0.591 Hom.: 5957

Bravo AF: 0.540

Asia WGS AF: 0.519 AC: 1807 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	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.61

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: rs3741128; hg19: chr11-74203004;