12-6385074-A-G

Variant names:

• chr12-6385074-A-G
• rs41480749
• NM_002342.3:c.246A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002342.3(LTBR):​c.246A>G​(p.Thr82Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,614,226 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (6 hom., cov: 32)
  • Exomes 𝑓: 0.011 (92 hom.)
• Consequence: LTBR NM_002342.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21
• Publications: 2 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 12-6385074-A-G is Benign according to our data. Variant chr12-6385074-A-G is described in ClinVar as Benign. ClinVar VariationId is 773257.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.21 with no splicing effect.
• BS2: High AC in GnomAd4 at 1097 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002342.3. 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
	LTBR	NM_002342.3	MANE Select	c.246A>G	p.Thr82Thr	synonymous	Exon 3 of 10	NP_002333.1	P36941-1
	LTBR	NM_001414303.1		c.246A>G	p.Thr82Thr	synonymous	Exon 3 of 10	NP_001401232.1
	LTBR	NM_001414304.1		c.327A>G	p.Thr109Thr	synonymous	Exon 3 of 10	NP_001401233.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBR	ENST00000228918.9	TSL:1 MANE Select	c.246A>G	p.Thr82Thr	synonymous	Exon 3 of 10	ENSP00000228918.4	P36941-1
	LTBR	ENST00000884044.1		c.246A>G	p.Thr82Thr	synonymous	Exon 3 of 10	ENSP00000554103.1
	LTBR	ENST00000957634.1		c.327A>G	p.Thr109Thr	synonymous	Exon 3 of 10	ENSP00000627693.1

Frequencies

GnomAD3 genomes AF: 0.00721 AC: 1097 AN: 152220 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00822 AC: 2067 AN: 251494 AF XY: 0.00800

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.00853

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0188

Gnomad NFE exome AF: 0.0116

Gnomad OTH exome AF: 0.00814

GnomAD4 exome AF: 0.0107 AC: 15661 AN: 1461888 Hom.: 92 Cov.: 32 AF XY: 0.0105 AC XY: 7632 AN XY: 727244

African (AFR) AF: 0.00134 AC: 45 AN: 33480

American (AMR) AF: 0.00237 AC: 106 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00849 AC: 222 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00432 AC: 373 AN: 86258

European-Finnish (FIN) AF: 0.0173 AC: 924 AN: 53418

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.0121 AC: 13407 AN: 1112010

Other (OTH) AF: 0.00949 AC: 573 AN: 60394

GnomAD4 genome AF: 0.00720 AC: 1097 AN: 152338 Hom.: 6 Cov.: 32 AF XY: 0.00721 AC XY: 537 AN XY: 74496

African (AFR) AF: 0.00161 AC: 67 AN: 41572

American (AMR) AF: 0.00444 AC: 68 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4832

European-Finnish (FIN) AF: 0.0173 AC: 184 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0106 AC: 722 AN: 68030

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00978 Hom.: 21

Bravo AF: 0.00644

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00960

EpiControl AF: 0.00883

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.57
DANN	Benign	0.49
PhyloP100		-1.2
PromoterAI		-0.053	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=299/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs41480749; hg19: chr12-6494240; COSMIC: COSV57438960; COSMIC: COSV57438960;