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: Labcorp Genetics (formerly Invitae), Orphanet
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LITAF	XM_011522754.4	c.85+35636A>G		intron_variant	Intron 3 of 5		XP_011521056.1
LITAF	XM_047434926.1	c.85+35636A>G		intron_variant	Intron 2 of 4		XP_047290882.1
LITAF	XM_047434927.1	c.85+35636A>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+31226A>G		intron_variant	Intron 1 of 3	4		ENSP00000461667.1
LITAF	ENST00000571627.5	c.-6+491A>G		intron_variant	Intron 1 of 3	4		ENSP00000460743.1
LITAF	ENST00000574848.5	c.85+35636A>G		intron_variant	Intron 3 of 3	4		ENSP00000459898.1
LITAF	ENST00000576334.1	c.85+35636A>G		intron_variant	Intron 3 of 3	4		ENSP00000458538.1

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 v4.3

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

Other links and lift over

dbSNP: rs8049607; hg19: chr16-11691753;