12-6385291-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002342.3(LTBR):c.384G>A(p.Pro128=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000691 in 1,614,082 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (4 hom.)
• Consequence: LTBR NM_002342.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.65

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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 12-6385291-G-A is Benign according to our data. Variant chr12-6385291-G-A is described in ClinVar as [Benign]. Clinvar id is 723535.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.65 with no splicing effect.
• BS2: High AC in GnomAd at 572 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTBR	NM_002342.3	c.384G>A	p.Pro128=	synonymous_variant	4/10	ENST00000228918.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTBR	ENST00000228918.9	c.384G>A	p.Pro128=	synonymous_variant	4/10	1	NM_002342.3	P2

Frequencies

GnomAD3 genomes AF: 0.00376 AC: 572 AN: 152120 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000959

GnomAD3 exomes AF: 0.000895 AC: 225 AN: 251396 Hom.: 0 AF XY: 0.000655 AC XY: 89 AN XY: 135884

Gnomad AFR exome AF: 0.0118

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000615

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000371 AC: 543 AN: 1461844 Hom.: 4 Cov.: 32 AF XY: 0.000356 AC XY: 259 AN XY: 727226

Gnomad4 AFR exome AF: 0.0120

Gnomad4 AMR exome AF: 0.000671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000558

Gnomad4 OTH exome AF: 0.000729

GnomAD4 genome AF: 0.00376 AC: 572 AN: 152238 Hom.: 3 Cov.: 32 AF XY: 0.00360 AC XY: 268 AN XY: 74446

Gnomad4 AFR AF: 0.0130

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.00192 Hom.: 2

Bravo AF: 0.00407

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 05, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	4.0
Dann	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs41489647; hg19: chr12-6494457;