12-6382781-C-T

Variant names:

• chr12-6382781-C-T
• rs3759333
• NM_001270987.2:c.40-1807C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270987.2(LTBR):​c.40-1807C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,082 control chromosomes in the GnomAD database, including 6,710 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 0.29 (6710 hom., cov: 32)
• Consequence: LTBR NM_001270987.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 16 publications found

Genes affected

LTBR (HGNC:6718): (lymphotoxin beta receptor) This gene encodes a member of the tumor necrosis factor receptor superfamily. The major ligands of this receptor include lymphotoxin alpha/beta and tumor necrosis factor ligand superfamily member 14. The encoded protein plays a role in signalling during the development of lymphoid and other organs, lipid metabolism, immune response, and programmed cell death. Activity of this receptor has also been linked to carcinogenesis. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270987.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBR	NM_001270987.2		c.40-1807C>T		intron	N/A	NP_001257916.1
	LTBR	NM_001414309.1		c.40-1807C>T		intron	N/A	NP_001401238.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBR	ENST00000539925.5	TSL:2	c.40-1807C>T		intron	N/A	ENSP00000440875.1
	LTBR	ENST00000542830.5	TSL:4	n.266-1807C>T		intron	N/A
	LTBR	ENST00000546296.5	TSL:4	n.551-1807C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43403 AN: 151964 Hom.: 6697 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.286

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.286 AC: 43461 AN: 152082 Hom.: 6710 Cov.: 32 AF XY: 0.284 AC XY: 21107 AN XY: 74364

African (AFR) AF: 0.390 AC: 16192 AN: 41468

American (AMR) AF: 0.245 AC: 3752 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 812 AN: 3464

East Asian (EAS) AF: 0.431 AC: 2228 AN: 5164

South Asian (SAS) AF: 0.233 AC: 1125 AN: 4824

European-Finnish (FIN) AF: 0.204 AC: 2161 AN: 10574

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.239 AC: 16238 AN: 67986

Other (OTH) AF: 0.287 AC: 605 AN: 2110

Alfa AF: 0.252 Hom.: 9160

Bravo AF: 0.295

Asia WGS AF: 0.313 AC: 1092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.95
DANN	Benign	0.72
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3759333; hg19: chr12-6491947;