rs735951

Variant names:

• chr16-11599680-G-A
• rs735951
• ENST00000576036.5:c.-6+29443C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-11599680-G-A
• chr16-11599680-G-C
• chr16-11599680-G-T

Variant summary

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

The ENST00000576036.5(LITAF):​c.-6+29443C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,770 control chromosomes in the GnomAD database, including 15,606 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 0.45 (15606 hom., cov: 30)
• Consequence: LITAF ENST00000576036.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 25 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 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+29443C>T		intron	N/A	ENSP00000461667.1	Q99732-1
	LITAF	ENST00000888115.1		c.-6+33853C>T		intron	N/A	ENSP00000558174.1
	LITAF	ENST00000888116.1		c.-6+36145C>T		intron	N/A	ENSP00000558175.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68480 AN: 151652 Hom.: 15603 Cov.: 30

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.451 AC: 68520 AN: 151770 Hom.: 15606 Cov.: 30 AF XY: 0.447 AC XY: 33152 AN XY: 74152

African (AFR) AF: 0.445 AC: 18408 AN: 41376

American (AMR) AF: 0.423 AC: 6447 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1544 AN: 3468

East Asian (EAS) AF: 0.540 AC: 2779 AN: 5148

South Asian (SAS) AF: 0.400 AC: 1923 AN: 4808

European-Finnish (FIN) AF: 0.421 AC: 4431 AN: 10520

Middle Eastern (MID) AF: 0.524 AC: 153 AN: 292

European-Non Finnish (NFE) AF: 0.462 AC: 31388 AN: 67888

Other (OTH) AF: 0.472 AC: 994 AN: 2108

Alfa AF: 0.460 Hom.: 41690

Bravo AF: 0.454

Asia WGS AF: 0.458 AC: 1588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.4
DANN	Benign	0.61
PhyloP100		-0.11
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: rs735951;

hg19: chr16-11693536;