rs1267844279

Variant names:

• chr6-47234839-G-A
• rs1267844279
• NM_014452.5:c.1569C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-47234839-G-A
• chr6-47234839-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014452.5(TNFRSF21):​c.1569C>T​(p.Ile523Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,376,840 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: TNFRSF21 NM_014452.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427
• Publications: 2 publications found

Genes affected

TNFRSF21 (HGNC:13469): (TNF receptor superfamily member 21) This gene encodes a member of the tumor necrosis factor receptor superfamily. The encoded protein activates nuclear factor kappa-B and mitogen-activated protein kinase 8 (also called c-Jun N-terminal kinase 1), and induces cell apoptosis. Through its death domain, the encoded receptor interacts with tumor necrosis factor receptor type 1-associated death domain (TRADD) protein, which is known to mediate signal transduction of tumor necrosis factor receptors. Knockout studies in mice suggest that this gene plays a role in T-helper cell activation, and may be involved in inflammation and immune regulation. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=-0.427 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF21	NM_014452.5	c.1569C>T	p.Ile523Ile	synonymous_variant	Exon 5 of 6	ENST00000296861.2	NP_055267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF21	ENST00000296861.2	c.1569C>T	p.Ile523Ile	synonymous_variant	Exon 5 of 6	1	NM_014452.5	ENSP00000296861.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1376840 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 678940

African (AFR) AF: 0.0000340 AC: 1 AN: 29374

American (AMR) AF: 0.00 AC: 0 AN: 29454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24168

East Asian (EAS) AF: 0.00 AC: 0 AN: 34026

South Asian (SAS) AF: 0.00 AC: 0 AN: 74062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073122

Other (OTH) AF: 0.00 AC: 0 AN: 56920

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.3
DANN	Benign	0.68
PhyloP100		-0.43

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: rs1267844279; hg19: chr6-47202575;