6-31581779-T-G

Position:

• chr6-31581779-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002341.2(LTB):​c.208+35A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 1,611,984 control chromosomes in the GnomAD database, including 3,821 homozygotes. 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 0.066 (351 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3470 hom.)
• Consequence: LTB NM_002341.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

Genes affected

LTB (HGNC:6711): (lymphotoxin beta) Lymphotoxin beta is a type II membrane protein of the TNF family. It anchors lymphotoxin-alpha to the cell surface through heterotrimer formation. The predominant form on the lymphocyte surface is the lymphotoxin-alpha 1/beta 2 complex (e.g. 1 molecule alpha/2 molecules beta) and this complex is the primary ligand for the lymphotoxin-beta receptor. The minor complex is lymphotoxin-alpha 2/beta 1. LTB is an inducer of the inflammatory response system and involved in normal development of lymphoid tissue. Lymphotoxin-beta isoform b is unable to complex with lymphotoxin-alpha suggesting a function for lymphotoxin-beta which is independent of lympyhotoxin-alpha. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

LTB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTB	NM_002341.2	c.208+35A>C		intron_variant		ENST00000429299.3	NP_002332.1
LTB	NM_009588.1	c.163-149A>C		intron_variant			NP_033666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTB	ENST00000429299.3	c.208+35A>C		intron_variant		1	NM_002341.2	ENSP00000410481.3
LTB	ENST00000446745.2	c.163-149A>C		intron_variant		1		ENSP00000416113.2
LTB	ENST00000482429.1	n.628A>C		non_coding_transcript_exon_variant	1/2	2
LTB	ENST00000483972.1	n.28-149A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0656 AC: 9973 AN: 151918 Hom.: 348 Cov.: 32

Gnomad AFR AF: 0.0725

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0347

Gnomad SAS AF: 0.0838

Gnomad FIN AF: 0.0181

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0656

Gnomad OTH AF: 0.0790

GnomAD3 exomes AF: 0.0604 AC: 14856 AN: 245890 Hom.: 577 AF XY: 0.0627 AC XY: 8398 AN XY: 134042

Gnomad AFR exome AF: 0.0715

Gnomad AMR exome AF: 0.0540

Gnomad ASJ exome AF: 0.124

Gnomad EAS exome AF: 0.0320

Gnomad SAS exome AF: 0.0778

Gnomad FIN exome AF: 0.0175

Gnomad NFE exome AF: 0.0634

Gnomad OTH exome AF: 0.0624

GnomAD4 exome AF: 0.0645 AC: 94148 AN: 1459948 Hom.: 3470 Cov.: 32 AF XY: 0.0653 AC XY: 47421 AN XY: 726296

Gnomad4 AFR exome AF: 0.0710

Gnomad4 AMR exome AF: 0.0568

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.0284

Gnomad4 SAS exome AF: 0.0780

Gnomad4 FIN exome AF: 0.0218

Gnomad4 NFE exome AF: 0.0646

Gnomad4 OTH exome AF: 0.0765

GnomAD4 genome AF: 0.0658 AC: 9997 AN: 152036 Hom.: 351 Cov.: 32 AF XY: 0.0642 AC XY: 4774 AN XY: 74312

Gnomad4 AFR AF: 0.0730

Gnomad4 AMR AF: 0.0618

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0347

Gnomad4 SAS AF: 0.0831

Gnomad4 FIN AF: 0.0181

Gnomad4 NFE AF: 0.0656

Gnomad4 OTH AF: 0.0782

Alfa AF: 0.0410 Hom.: 95

Bravo AF: 0.0695

Asia WGS AF: 0.0600 AC: 207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs3093553; hg19: chr6-31549556;