NM_001136472.2:c.*1251A>T

Variant names:

• chr16-11548386-T-A
• rs7102
• NM_001136472.2:c.*1251A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001136472.2(LITAF):​c.*1251A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LITAF NM_001136472.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 24 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LITAF	NM_001136472.2	c.*1251A>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000622633.5	NP_001129944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LITAF	ENST00000622633.5	c.*1251A>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_001136472.2	ENSP00000483114.1
LITAF	ENST00000339430.9	c.*1251A>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000340118.5
LITAF	ENST00000571688.6	c.*1251A>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000459533.1
LITAF	ENST00000413364.6	c.*1376A>T		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000397958.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 301784 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 171990

African (AFR) AF: 0.00 AC: 0 AN: 8554

American (AMR) AF: 0.00 AC: 0 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10786

East Asian (EAS) AF: 0.00 AC: 0 AN: 9210

South Asian (SAS) AF: 0.00 AC: 0 AN: 59650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1150

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 158754

Other (OTH) AF: 0.00 AC: 0 AN: 14042

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.35
DANN	Benign	0.52
PhyloP100		-1.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7102; hg19: chr16-11642242;