16-11548386-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001136472.2(LITAF):​c.*1251A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 453,582 control chromosomes in the GnomAD database, including 32,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10708 hom., cov: 31)
  • Exomes 𝑓: 0.38 (22162 hom.)
• Consequence: LITAF NM_001136472.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-11548386-T-C is Benign according to our data. Variant chr16-11548386-T-C is described in ClinVar as Benign. ClinVar VariationId is 317757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136472.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LITAF	NM_001136472.2	MANE Select	c.*1251A>G		3_prime_UTR	Exon 4 of 4	NP_001129944.1	Q99732-1
	LITAF	NM_004862.4		c.*1251A>G		3_prime_UTR	Exon 4 of 4	NP_004853.2	Q99732-1
	LITAF	NM_001136473.1		c.*1376A>G		3_prime_UTR	Exon 5 of 5	NP_001129945.1	Q99732-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LITAF	ENST00000622633.5	TSL:1 MANE Select	c.*1251A>G		3_prime_UTR	Exon 4 of 4	ENSP00000483114.1	Q99732-1
	LITAF	ENST00000339430.9	TSL:1	c.*1251A>G		3_prime_UTR	Exon 4 of 4	ENSP00000340118.5	Q99732-1
	LITAF	ENST00000571688.6	TSL:1	c.*1251A>G		3_prime_UTR	Exon 4 of 4	ENSP00000459533.1	Q99732-1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56458 AN: 151692 Hom.: 10693 Cov.: 31

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.355

GnomAD2 exomes AF: 0.388 AC: 50577 AN: 130444 AF XY: 0.391

Gnomad AFR exome AF: 0.399

Gnomad AMR exome AF: 0.358

Gnomad ASJ exome AF: 0.407

Gnomad EAS exome AF: 0.535

Gnomad FIN exome AF: 0.338

Gnomad NFE exome AF: 0.362

Gnomad OTH exome AF: 0.370

GnomAD4 exome AF: 0.381 AC: 114843 AN: 301770 Hom.: 22162 Cov.: 0 AF XY: 0.386 AC XY: 66371 AN XY: 171986

African (AFR) AF: 0.398 AC: 3406 AN: 8554

American (AMR) AF: 0.358 AC: 9768 AN: 27272

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 4408 AN: 10786

East Asian (EAS) AF: 0.533 AC: 4912 AN: 9210

South Asian (SAS) AF: 0.418 AC: 24911 AN: 59646

European-Finnish (FIN) AF: 0.339 AC: 4189 AN: 12364

Middle Eastern (MID) AF: 0.374 AC: 430 AN: 1150

European-Non Finnish (NFE) AF: 0.363 AC: 57581 AN: 158750

Other (OTH) AF: 0.373 AC: 5238 AN: 14038

GnomAD4 genome AF: 0.372 AC: 56518 AN: 151812 Hom.: 10708 Cov.: 31 AF XY: 0.373 AC XY: 27638 AN XY: 74166

African (AFR) AF: 0.390 AC: 16135 AN: 41380

American (AMR) AF: 0.331 AC: 5046 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1371 AN: 3468

East Asian (EAS) AF: 0.520 AC: 2680 AN: 5156

South Asian (SAS) AF: 0.425 AC: 2040 AN: 4804

European-Finnish (FIN) AF: 0.327 AC: 3437 AN: 10524

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.364 AC: 24706 AN: 67930

Other (OTH) AF: 0.362 AC: 765 AN: 2112

Alfa AF: 0.365 Hom.: 13678

Bravo AF: 0.375

Asia WGS AF: 0.496 AC: 1726 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Charcot-Marie-Tooth disease type 1C (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.44
DANN	Benign	0.43
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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;