rs7187810

Variant names:

• chr16-11548821-A-T
• rs7187810
• NM_001136472.2:c.*816T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001136472.2(LITAF):​c.*816T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 450,504 control chromosomes in the GnomAD database, including 302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (246 hom., cov: 31)
  • Exomes 𝑓: 0.0058 (56 hom.)
• Consequence: LITAF NM_001136472.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.13
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 16-11548821-A-T is Benign according to our data. Variant chr16-11548821-A-T is described in ClinVar as Benign. ClinVar VariationId is 317764.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 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.*816T>A		3_prime_UTR	Exon 4 of 4	NP_001129944.1	Q99732-1
	LITAF	NM_004862.4		c.*816T>A		3_prime_UTR	Exon 4 of 4	NP_004853.2	Q99732-1
	LITAF	NM_001136473.1		c.*941T>A		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.*816T>A		3_prime_UTR	Exon 4 of 4	ENSP00000483114.1	Q99732-1
	LITAF	ENST00000339430.9	TSL:1	c.*816T>A		3_prime_UTR	Exon 4 of 4	ENSP00000340118.5	Q99732-1
	LITAF	ENST00000571688.6	TSL:1	c.*816T>A		3_prime_UTR	Exon 4 of 4	ENSP00000459533.1	Q99732-1

Frequencies

GnomAD3 genomes AF: 0.0319 AC: 4820 AN: 151206 Hom.: 246 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.00271

Gnomad FIN AF: 0.00423

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.0213

GnomAD2 exomes AF: 0.00816 AC: 1042 AN: 127772 AF XY: 0.00708

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.00588

Gnomad ASJ exome AF: 0.000629

Gnomad EAS exome AF: 0.000590

Gnomad FIN exome AF: 0.00656

Gnomad NFE exome AF: 0.00282

Gnomad OTH exome AF: 0.00586

GnomAD4 exome AF: 0.00579 AC: 1733 AN: 299184 Hom.: 56 Cov.: 0 AF XY: 0.00494 AC XY: 843 AN XY: 170820

African (AFR) AF: 0.107 AC: 881 AN: 8236

American (AMR) AF: 0.00609 AC: 161 AN: 26448

Ashkenazi Jewish (ASJ) AF: 0.000187 AC: 2 AN: 10674

East Asian (EAS) AF: 0.000652 AC: 6 AN: 9204

South Asian (SAS) AF: 0.00218 AC: 129 AN: 59156

European-Finnish (FIN) AF: 0.00527 AC: 65 AN: 12332

Middle Eastern (MID) AF: 0.0106 AC: 12 AN: 1136

European-Non Finnish (NFE) AF: 0.00206 AC: 326 AN: 158104

Other (OTH) AF: 0.0109 AC: 151 AN: 13894

GnomAD4 genome AF: 0.0319 AC: 4824 AN: 151320 Hom.: 246 Cov.: 31 AF XY: 0.0317 AC XY: 2343 AN XY: 73978

African (AFR) AF: 0.107 AC: 4403 AN: 41230

American (AMR) AF: 0.0117 AC: 178 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5156

South Asian (SAS) AF: 0.00272 AC: 13 AN: 4784

European-Finnish (FIN) AF: 0.00423 AC: 44 AN: 10408

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00190 AC: 129 AN: 67766

Other (OTH) AF: 0.0215 AC: 45 AN: 2090

Alfa AF: 0.0150 Hom.: 21

Bravo AF: 0.0364

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Charcot-Marie-Tooth disease type 1C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.15
PhyloP100		-1.1
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: rs7187810; hg19: chr16-11642677; COSMIC: COSV59655574; COSMIC: COSV59655574;