16-11547324-A-G

Variant names:

• chr16-11547324-A-G
• rs7203193
• ENST00000571688.6:c.*2313T>C

Variant summary

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

The ENST00000571688.6(LITAF):​c.*2313T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,168 control chromosomes in the GnomAD database, including 24,466 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 0.55 (24466 hom., cov: 33)
• Consequence: LITAF ENST00000571688.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000571688.6. 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	ENST00000571688.6	TSL:1	c.*2313T>C		3_prime_UTR	Exon 4 of 4	ENSP00000459533.1	Q99732-1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83672 AN: 152048 Hom.: 24427 Cov.: 33

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.551 AC: 83778 AN: 152168 Hom.: 24466 Cov.: 33 AF XY: 0.547 AC XY: 40664 AN XY: 74384

African (AFR) AF: 0.769 AC: 31932 AN: 41512

American (AMR) AF: 0.435 AC: 6646 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1587 AN: 3472

East Asian (EAS) AF: 0.531 AC: 2754 AN: 5182

South Asian (SAS) AF: 0.435 AC: 2099 AN: 4826

European-Finnish (FIN) AF: 0.452 AC: 4780 AN: 10570

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32438 AN: 67996

Other (OTH) AF: 0.498 AC: 1052 AN: 2114

Alfa AF: 0.501 Hom.: 60599

Bravo AF: 0.562

Asia WGS AF: 0.540 AC: 1879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.30
PhyloP100		-0.54

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: rs7203193;

hg19: chr16-11641180;