NM_014452.5:c.1244-9358T>C

Variant names:

• chr6-47262879-A-G
• rs2103868
• NM_014452.5:c.1244-9358T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
TNFRSF21	NM_014452.5	c.1244-9358T>C		intron_variant	Intron 3 of 5	ENST00000296861.2	NP_055267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF21	ENST00000296861.2	c.1244-9358T>C		intron_variant	Intron 3 of 5	1	NM_014452.5	ENSP00000296861.2

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

African (AFR) AF: 0.0197 AC: 817 AN: 41570

American (AMR) AF: 0.0680 AC: 1039 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 373 AN: 3466

East Asian (EAS) AF: 0.204 AC: 1055 AN: 5172

South Asian (SAS) AF: 0.145 AC: 699 AN: 4824

European-Finnish (FIN) AF: 0.179 AC: 1893 AN: 10582

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0996 AC: 6774 AN: 68008

Other (OTH) AF: 0.0956 AC: 202 AN: 2114

Alfa AF: 0.0915 Hom.: 2322

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
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs2103868; hg19: chr6-47230615;