dbSNP rs774513067: LITAF:c.*1399C>T (chr16-11548238-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001136472.2(LITAF):c.*1399C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 301,790 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)

Exomes 𝑓: 0.0000033 ( 0 hom. )

Consequence

LITAF
NM_001136472.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.357

Publications

0 publications found

Variant links:

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

LITAF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LITAF	NM_001136472.2 link	c.*1399C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000622633.5	NP_001129944.1	Q99732-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LITAF	ENST00000622633.5 link	c.*1399C>T	3_prime_UTR_variant	Exon 4 of 4	1	NM_001136472.2	ENSP00000483114.1	Q99732-1
LITAF	ENST00000339430.9 link	c.*1399C>T	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000340118.5	Q99732-1
LITAF	ENST00000571688.6 link	c.*1399C>T	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000459533.1	Q99732-1
LITAF	ENST00000413364.6 link	c.*1524C>T	3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000397958.2	Q99732-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000767

AC:

AN:

130420

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000331

AC:

AN:

301790

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

171994

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

8554

American (AMR)

AF:

0.00

AC:

AN:

27272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10786

East Asian (EAS)

AF:

0.00

AC:

AN:

9210

South Asian (SAS)

AF:

0.0000168

AC:

AN:

59650

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1150

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

158764

Other (OTH)

AF:

0.00

AC:

AN:

14040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.6

(source)

DANN

Benign

0.42

PhyloP100

0.36

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over