rs34448402

Variant names:

• chr16-11553577-G-A
• rs34448402
• NM_001136472.2:c.333C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-11553577-G-A
• chr16-11553577-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001136472.2(LITAF):​c.333C>T​(p.Ala111Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00311 in 1,614,134 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (9 hom.)
• Consequence: LITAF NM_001136472.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.44
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 16-11553577-G-A is Benign according to our data. Variant chr16-11553577-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 221057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.44 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00252 (383/152276) while in subpopulation AMR AF = 0.00366 (56/15292). AF 95% confidence interval is 0.00326. There are 1 homozygotes in GnomAd4. There are 166 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 383 AD gene.

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.333C>T	p.Ala111Ala	synonymous	Exon 3 of 4	NP_001129944.1	Q99732-1
	LITAF	NM_004862.4		c.333C>T	p.Ala111Ala	synonymous	Exon 3 of 4	NP_004853.2	Q99732-1
	LITAF	NM_001136473.1		c.333C>T	p.Ala111Ala	synonymous	Exon 3 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.333C>T	p.Ala111Ala	synonymous	Exon 3 of 4	ENSP00000483114.1	Q99732-1
	LITAF	ENST00000339430.9	TSL:1	c.333C>T	p.Ala111Ala	synonymous	Exon 3 of 4	ENSP00000340118.5	Q99732-1
	LITAF	ENST00000570904.5	TSL:1	c.333C>T	p.Ala111Ala	synonymous	Exon 3 of 4	ENSP00000459138.1	Q99732-1

Frequencies

GnomAD3 genomes AF: 0.00251 AC: 382 AN: 152158 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00362

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00213 AC: 536 AN: 251186 AF XY: 0.00227

Gnomad AFR exome AF: 0.000924

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000463

Gnomad NFE exome AF: 0.00352

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00317 AC: 4641 AN: 1461858 Hom.: 9 Cov.: 31 AF XY: 0.00311 AC XY: 2262 AN XY: 727226

African (AFR) AF: 0.000418 AC: 14 AN: 33480

American (AMR) AF: 0.00170 AC: 76 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00264 AC: 69 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000522 AC: 45 AN: 86254

European-Finnish (FIN) AF: 0.000524 AC: 28 AN: 53404

Middle Eastern (MID) AF: 0.00381 AC: 22 AN: 5768

European-Non Finnish (NFE) AF: 0.00378 AC: 4208 AN: 1111998

Other (OTH) AF: 0.00296 AC: 179 AN: 60396

GnomAD4 genome AF: 0.00252 AC: 383 AN: 152276 Hom.: 1 Cov.: 32 AF XY: 0.00223 AC XY: 166 AN XY: 74458

African (AFR) AF: 0.00106 AC: 44 AN: 41552

American (AMR) AF: 0.00366 AC: 56 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00363 AC: 247 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00323 Hom.: 0

Bravo AF: 0.00277

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00420

EpiControl AF: 0.00468

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Charcot-Marie-Tooth disease type 1C (3)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Charcot-Marie-Tooth disease (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.9
DANN	Benign	0.45
PhyloP100		-1.4
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs34448402; hg19: chr16-11647433;