chr6-47262879-A-G

Position:

• chr6-47262879-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014452.5(TNFRSF21):​c.1244-9358T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 152,230 control chromosomes in the GnomAD database, including 765 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 0.086 (765 hom., cov: 32)
• Consequence: TNFRSF21 NM_014452.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF21	NM_014452.5	c.1244-9358T>C		intron_variant		ENST00000296861.2	NP_055267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF21	ENST00000296861.2	c.1244-9358T>C		intron_variant		1	NM_014452.5	ENSP00000296861	P1

Frequencies

GnomAD3 genomes AF: 0.0859 AC: 13061 AN: 152112 Hom.: 762 Cov.: 32

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.0680

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0996

Gnomad OTH AF: 0.0908

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

GnomAD4 genome AF: 0.0859 AC: 13070 AN: 152230 Hom.: 765 Cov.: 32 AF XY: 0.0916 AC XY: 6816 AN XY: 74428

Gnomad4 AFR AF: 0.0197

Gnomad4 AMR AF: 0.0680

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.0996

Gnomad4 OTH AF: 0.0956

Alfa AF: 0.0975 Hom.: 1785

Bravo AF: 0.0745

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.37

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: rs2103868; hg19: chr6-47230615;