rs942172049

Variant names:

• chr16-11548420-T-C
• rs942172049
• NM_001136472.2:c.*1217A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-11548420-T-C
• chr16-11548420-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001136472.2(LITAF):​c.*1217A>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 0.0000176 in 453,864 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: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000099 (0 hom.)
• Consequence: LITAF NM_001136472.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.626
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000329 (5/152088) while in subpopulation AFR AF = 0.000121 (5/41412). AF 95% confidence interval is 0.0000474. There are 0 homozygotes in GnomAd4. There are 3 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LITAF	NM_001136472.2	c.*1217A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000622633.5	NP_001129944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LITAF	ENST00000622633.5	c.*1217A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_001136472.2	ENSP00000483114.1
LITAF	ENST00000339430.9	c.*1217A>G		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000340118.5
LITAF	ENST00000571688.6	c.*1217A>G		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000459533.1
LITAF	ENST00000413364.6	c.*1342A>G		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000397958.2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152088 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000230 AC: 3 AN: 130432 AF XY: 0.0000140

Gnomad AFR exome AF: 0.000164

Gnomad AMR exome AF: 0.0000411

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000959

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000994 AC: 3 AN: 301776 Hom.: 0 Cov.: 0 AF XY: 0.00000581 AC XY: 1 AN XY: 171984

African (AFR) AF: 0.000117 AC: 1 AN: 8552

American (AMR) AF: 0.0000367 AC: 1 AN: 27272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10786

East Asian (EAS) AF: 0.000109 AC: 1 AN: 9210

South Asian (SAS) AF: 0.00 AC: 0 AN: 59644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1150

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 158756

Other (OTH) AF: 0.00 AC: 0 AN: 14042

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152088 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74288

African (AFR) AF: 0.000121 AC: 5 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.61
PhyloP100		-0.63

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: rs942172049; hg19: chr16-11642276;