chr16-11548841-A-G

Variant names:

• chr16-11548841-A-G
• rs1198
• NM_001136472.2:c.*796T>C

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.*796T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 453,402 control chromosomes in the GnomAD database, including 5,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2720 hom., cov: 31)
  • Exomes 𝑓: 0.13 (2775 hom.)
• Consequence: LITAF NM_001136472.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.919
• Publications: 16 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=-0.86).
• BP6: Variant 16-11548841-A-G is Benign according to our data. Variant chr16-11548841-A-G is described in ClinVar as Benign. ClinVar VariationId is 317765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 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.*796T>C		3_prime_UTR	Exon 4 of 4	NP_001129944.1	Q99732-1
	LITAF	NM_004862.4		c.*796T>C		3_prime_UTR	Exon 4 of 4	NP_004853.2	Q99732-1
	LITAF	NM_001136473.1		c.*921T>C		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.*796T>C		3_prime_UTR	Exon 4 of 4	ENSP00000483114.1	Q99732-1
	LITAF	ENST00000339430.9	TSL:1	c.*796T>C		3_prime_UTR	Exon 4 of 4	ENSP00000340118.5	Q99732-1
	LITAF	ENST00000571688.6	TSL:1	c.*796T>C		3_prime_UTR	Exon 4 of 4	ENSP00000459533.1	Q99732-1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27020 AN: 151818 Hom.: 2718 Cov.: 31

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0925

Gnomad SAS AF: 0.0932

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.153

GnomAD2 exomes AF: 0.122 AC: 15950 AN: 130224 AF XY: 0.120

Gnomad AFR exome AF: 0.288

Gnomad AMR exome AF: 0.0753

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.0910

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.128 AC: 38634 AN: 301466 Hom.: 2775 Cov.: 0 AF XY: 0.123 AC XY: 21219 AN XY: 171822

African (AFR) AF: 0.289 AC: 2452 AN: 8488

American (AMR) AF: 0.0759 AC: 2066 AN: 27226

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 1185 AN: 10776

East Asian (EAS) AF: 0.0886 AC: 816 AN: 9210

South Asian (SAS) AF: 0.0970 AC: 5776 AN: 59526

European-Finnish (FIN) AF: 0.157 AC: 1942 AN: 12364

Middle Eastern (MID) AF: 0.134 AC: 154 AN: 1150

European-Non Finnish (NFE) AF: 0.141 AC: 22301 AN: 158698

Other (OTH) AF: 0.138 AC: 1942 AN: 14028

GnomAD4 genome AF: 0.178 AC: 27040 AN: 151936 Hom.: 2720 Cov.: 31 AF XY: 0.176 AC XY: 13075 AN XY: 74270

African (AFR) AF: 0.287 AC: 11875 AN: 41402

American (AMR) AF: 0.117 AC: 1788 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3470

East Asian (EAS) AF: 0.0931 AC: 481 AN: 5164

South Asian (SAS) AF: 0.0924 AC: 445 AN: 4816

European-Finnish (FIN) AF: 0.170 AC: 1794 AN: 10552

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9746 AN: 67968

Other (OTH) AF: 0.153 AC: 323 AN: 2106

Alfa AF: 0.177 Hom.: 1690

Bravo AF: 0.179

Asia WGS AF: 0.139 AC: 482 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	-0.86
CADD	Benign	4.0
DANN	Benign	0.47
PhyloP100		0.92
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: rs1198; hg19: chr16-11642697;