chr6-47298960-A-C

Variant names:

• chr6-47298960-A-C
• rs2103867
• NM_014452.5:c.96+10456T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014452.5(TNFRSF21):​c.96+10456T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 152,284 control chromosomes in the GnomAD database, including 67,525 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 0.94 (67525 hom., cov: 32)
• Consequence: TNFRSF21 NM_014452.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871
• Publications: 4 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]

TNFRSF21 Gene-Disease associations (from GenCC):

• myopia

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014452.5. 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
	TNFRSF21	NM_014452.5	MANE Select	c.96+10456T>G		intron	N/A	NP_055267.1	O75509

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF21	ENST00000296861.2	TSL:1 MANE Select	c.96+10456T>G		intron	N/A	ENSP00000296861.2	O75509
	TNFRSF21	ENST00000877798.1		c.96+10456T>G		intron	N/A	ENSP00000547857.1
	TNFRSF21	ENST00000952536.1		c.96+10456T>G		intron	N/A	ENSP00000622595.1

Frequencies

GnomAD3 genomes AF: 0.941 AC: 143169 AN: 152166 Hom.: 67464 Cov.: 32

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.919

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.966

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.912

Gnomad OTH AF: 0.924

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

GnomAD4 genome AF: 0.941 AC: 143290 AN: 152284 Hom.: 67525 Cov.: 32 AF XY: 0.943 AC XY: 70232 AN XY: 74458

African (AFR) AF: 0.985 AC: 40950 AN: 41554

American (AMR) AF: 0.938 AC: 14346 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.919 AC: 3191 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5177 AN: 5180

South Asian (SAS) AF: 0.966 AC: 4661 AN: 4826

European-Finnish (FIN) AF: 0.940 AC: 9962 AN: 10600

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.912 AC: 62067 AN: 68032

Other (OTH) AF: 0.925 AC: 1955 AN: 2114

Alfa AF: 0.924 Hom.: 63294

Bravo AF: 0.942

Asia WGS AF: 0.984 AC: 3421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.073
DANN	Benign	0.32
PhyloP100		-0.87
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: rs2103867; hg19: chr6-47266696;