6-31581779-T-G

Variant names:

• chr6-31581779-T-G
• rs3093553
• NM_002341.2:c.208+35A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002341.2. 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
	LTB	NM_002341.2	MANE Select	c.208+35A>C		intron	N/A	NP_002332.1	Q5STB2
	LTB	NM_009588.1		c.163-149A>C		intron	N/A	NP_033666.1	Q06643-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTB	ENST00000429299.3	TSL:1 MANE Select	c.208+35A>C		intron	N/A	ENSP00000410481.3	Q06643-1
	LTB	ENST00000446745.2	TSL:1	c.163-149A>C		intron	N/A	ENSP00000416113.2	Q06643-2
	LTB	ENST00000482429.1	TSL:2	n.628A>C		non_coding_transcript_exon	Exon 1 of 2

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

GnomAD2 exomes AF: 0.0604 AC: 14856 AN: 245890 AF XY: 0.0627

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 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

African (AFR) AF: 0.0710 AC: 2375 AN: 33460

American (AMR) AF: 0.0568 AC: 2537 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 3315 AN: 26070

East Asian (EAS) AF: 0.0284 AC: 1127 AN: 39698

South Asian (SAS) AF: 0.0780 AC: 6721 AN: 86218

European-Finnish (FIN) AF: 0.0218 AC: 1140 AN: 52278

Middle Eastern (MID) AF: 0.0909 AC: 524 AN: 5764

European-Non Finnish (NFE) AF: 0.0646 AC: 71795 AN: 1111490

Other (OTH) AF: 0.0765 AC: 4614 AN: 60328

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

African (AFR) AF: 0.0730 AC: 3026 AN: 41446

American (AMR) AF: 0.0618 AC: 945 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3468

East Asian (EAS) AF: 0.0347 AC: 179 AN: 5152

South Asian (SAS) AF: 0.0831 AC: 400 AN: 4816

European-Finnish (FIN) AF: 0.0181 AC: 192 AN: 10592

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

European-Non Finnish (NFE) AF: 0.0656 AC: 4458 AN: 67956

Other (OTH) AF: 0.0782 AC: 165 AN: 2110

Alfa AF: 0.0357 Hom.: 172

Bravo AF: 0.0695

Asia WGS AF: 0.0600 AC: 207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		-0.26
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: rs3093553; hg19: chr6-31549556;