rs735951

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LITAF	XM_011522754.4	c.85+33853C>T		intron_variant			XP_011521056.1
LITAF	XM_047434926.1	c.85+33853C>T		intron_variant			XP_047290882.1
LITAF	XM_047434927.1	c.85+33853C>T		intron_variant			XP_047290883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LITAF	ENST00000576036.5	c.-6+29443C>T		intron_variant		4		ENSP00000461667.1
LITAF	ENST00000574848.5	c.85+33853C>T		intron_variant		4		ENSP00000459898.1
LITAF	ENST00000576334.1	c.85+33853C>T		intron_variant		4		ENSP00000458538.1

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

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.472

Alfa AF: 0.462 Hom.: 28853

Bravo AF: 0.454

Asia WGS AF: 0.458 AC: 1588 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	4.4
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs735951; hg19: chr16-11693536;