rs13333308

Variant names:

• chr16-11607793-T-C
• rs13333308
• ENST00000576036.5:c.-6+21330A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000576036.5(LITAF):​c.-6+21330A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 152,238 control chromosomes in the GnomAD database, including 291 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.033 (291 hom., cov: 32)
• Consequence: LITAF ENST00000576036.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831
• Publications: 3 publications found

Genes affected

LITAF (HGNC:16841): (lipopolysaccharide induced TNF factor) Lipopolysaccharide is a potent stimulator of monocytes and macrophages, causing secretion of tumor necrosis factor-alpha (TNF-alpha) and other inflammatory mediators. This gene encodes lipopolysaccharide-induced TNF-alpha factor, which is a DNA-binding protein and can mediate the TNF-alpha expression by direct binding to the promoter region of the TNF-alpha gene. The transcription of this gene is induced by tumor suppressor p53 and has been implicated in the p53-induced apoptotic pathway. Mutations in this gene cause Charcot-Marie-Tooth disease type 1C (CMT1C) and may be involved in the carcinogenesis of extramammary Paget's disease (EMPD). Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2014]

LITAF Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease type 1C

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• Charcot-Marie-Tooth disease

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LITAF	XM_011522754.4	c.85+25740A>G		intron_variant	Intron 3 of 5		XP_011521056.1
LITAF	XM_047434926.1	c.85+25740A>G		intron_variant	Intron 2 of 4		XP_047290882.1
LITAF	XM_047434927.1	c.85+25740A>G		intron_variant	Intron 3 of 5		XP_047290883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LITAF	ENST00000576036.5	c.-6+21330A>G		intron_variant	Intron 1 of 3	4		ENSP00000461667.1
LITAF	ENST00000574848.5	c.85+25740A>G		intron_variant	Intron 3 of 3	4		ENSP00000459898.1
LITAF	ENST00000576334.1	c.85+25740A>G		intron_variant	Intron 3 of 3	4		ENSP00000458538.1

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4943 AN: 152120 Hom.: 289 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00957

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0278

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

GnomAD4 genome AF: 0.0325 AC: 4949 AN: 152238 Hom.: 291 Cov.: 32 AF XY: 0.0316 AC XY: 2354 AN XY: 74448

African (AFR) AF: 0.114 AC: 4717 AN: 41520

American (AMR) AF: 0.00955 AC: 146 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68026

Other (OTH) AF: 0.0275 AC: 58 AN: 2112

Alfa AF: 0.0522 Hom.: 160

Bravo AF: 0.0367

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.68
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs13333308; hg19: chr16-11701649;