rs8049607

Variant names:

• chr16-11597897-T-C
• rs8049607
• ENST00000576036.5:c.-6+31226A>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+31226A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 151,938 control chromosomes in the GnomAD database, including 19,586 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 0.50 (19586 hom., cov: 31)
• Consequence: LITAF ENST00000576036.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 58 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: Orphanet, Labcorp Genetics (formerly Invitae)
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000576036.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LITAF	ENST00000576036.5	TSL:4	c.-6+31226A>G		intron	N/A	ENSP00000461667.1	Q99732-1
	LITAF	ENST00000888115.1		c.-6+35636A>G		intron	N/A	ENSP00000558174.1
	LITAF	ENST00000888116.1		c.-6+37928A>G		intron	N/A	ENSP00000558175.1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76608 AN: 151820 Hom.: 19559 Cov.: 31

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.505 AC: 76683 AN: 151938 Hom.: 19586 Cov.: 31 AF XY: 0.501 AC XY: 37188 AN XY: 74262

African (AFR) AF: 0.554 AC: 22946 AN: 41442

American (AMR) AF: 0.461 AC: 7035 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1630 AN: 3462

East Asian (EAS) AF: 0.567 AC: 2929 AN: 5164

South Asian (SAS) AF: 0.471 AC: 2268 AN: 4820

European-Finnish (FIN) AF: 0.462 AC: 4876 AN: 10546

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33287 AN: 67932

Other (OTH) AF: 0.518 AC: 1096 AN: 2114

Alfa AF: 0.498 Hom.: 76449

Bravo AF: 0.508

Asia WGS AF: 0.520 AC: 1804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.68
DANN	Benign	0.73
PhyloP100		-0.0010
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs8049607;

hg19: chr16-11691753;