Genetic Variant LITAF:c.*816dupT (chr16-11548820-T-TA) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_001136472.2(LITAF):c.*816dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 451,982 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

LITAF
NM_001136472.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.13

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000264 (40/151230) while in subpopulation NFE AF = 0.000413 (28/67800). AF 95% confidence interval is 0.000293. There are 0 homozygotes in GnomAd4. There are 17 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position FAILED quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LITAF	NM_001136472.2 link	c.*816dupT		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 link	c.*816dupT	3_prime_UTR_variant	Exon 4 of 4	1	NM_001136472.2	ENSP00000483114.1	Q99732-1
LITAF	ENST00000339430 link	c.*816dupT	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000340118.5	Q99732-1
LITAF	ENST00000571688 link	c.*816dupT	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000459533.1	Q99732-1
LITAF	ENST00000413364 link	c.*941dupT	3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000397958.2	Q99732-3

Frequencies

GnomAD3 genomes

AF:

0.000264

AC:

AN:

151230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000413

Gnomad OTH

AF:

0.000482

GnomAD2 exomes

AF:

0.000201

AC:

AN:

129082

AF XY:

0.000255

show subpopulations

Gnomad AFR exome

AF:

0.000165

Gnomad AMR exome

AF:

0.0000416

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000385

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000186

AC:

AN:

300752

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

AN XY:

171462

show subpopulations

Gnomad4 AFR exome

AF:

0.000476

AC:

AN:

8404

Gnomad4 AMR exome

AF:

0.0000369

AC:

AN:

27066

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

10752

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

9208

Gnomad4 SAS exome

AF:

0.000135

AC:

AN:

59290

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

12352

Gnomad4 NFE exome

AF:

0.000265

AC:

AN:

158552

Gnomad4 Remaining exome

AF:

0.0000715

AC:

AN:

13982

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000264

AC:

AN:

151230

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

AN XY:

73830

show subpopulations

Gnomad4 AFR

AF:

0.000218

AC:

0.000218394

AN:

0.000218394

Gnomad4 AMR

AF:

0.000132

AC:

0.000132066

AN:

0.000132066

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000413

AC:

0.000412979

AN:

0.000412979

Gnomad4 OTH

AF:

0.000482

AC:

0.000481696

AN:

0.000481696

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000336

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease, type I

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over