rs12446552

Variant names:

• chr16-11626210-T-C
• rs12446552
• ENST00000576036.5:c.-6+2913A>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+2913A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,208 control chromosomes in the GnomAD database, including 3,280 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 0.18 (3280 hom., cov: 31)
• Consequence: LITAF ENST00000576036.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 10 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

ENSG00000300288 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LITAF	XM_011522754.4	c.85+7323A>G		intron_variant	Intron 3 of 5		XP_011521056.1
LITAF	XM_047434926.1	c.85+7323A>G		intron_variant	Intron 2 of 4		XP_047290882.1
LITAF	XM_047434927.1	c.85+7323A>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+2913A>G		intron_variant	Intron 1 of 3	4		ENSP00000461667.1
LITAF	ENST00000574848.5	c.85+7323A>G		intron_variant	Intron 3 of 3	4		ENSP00000459898.1
LITAF	ENST00000576334.1	c.85+7323A>G		intron_variant	Intron 3 of 3	4		ENSP00000458538.1
ENSG00000300288	ENST00000770627.1	n.*76T>C		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27439 AN: 152092 Hom.: 3281 Cov.: 31

Gnomad AFR AF: 0.0503

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.180 AC: 27430 AN: 152208 Hom.: 3280 Cov.: 31 AF XY: 0.174 AC XY: 12932 AN XY: 74396

African (AFR) AF: 0.0502 AC: 2084 AN: 41548

American (AMR) AF: 0.144 AC: 2208 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 879 AN: 3470

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5186

South Asian (SAS) AF: 0.120 AC: 578 AN: 4830

European-Finnish (FIN) AF: 0.223 AC: 2357 AN: 10572

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18619 AN: 68000

Other (OTH) AF: 0.178 AC: 375 AN: 2112

Alfa AF: 0.241 Hom.: 5562

Bravo AF: 0.167

Asia WGS AF: 0.0660 AC: 232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
DANN	Benign	0.31
PhyloP100		-1.3
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: rs12446552; hg19: chr16-11720066;