rs4872088

Variant names:

• chr8-23218667-G-A
• rs4872088
• NM_003844.4:c.306+6089C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-23218667-G-A
• chr8-23218667-G-C

Variant summary

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

The NM_003844.4(TNFRSF10A):​c.306+6089C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,950 control chromosomes in the GnomAD database, including 4,125 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 0.23 (4125 hom., cov: 31)
• Consequence: TNFRSF10A NM_003844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 2 publications found

Genes affected

TNFRSF10A (HGNC:11904): (TNF receptor superfamily member 10a) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL), and thus transduces cell death signal and induces cell apoptosis. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003844.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10A	NM_003844.4	MANE Select	c.306+6089C>T		intron	N/A	NP_003835.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10A	ENST00000221132.8	TSL:1 MANE Select	c.306+6089C>T		intron	N/A	ENSP00000221132.3
	TNFRSF10A	ENST00000613472.1	TSL:1	c.31+6364C>T		intron	N/A	ENSP00000480778.1
	TNFRSF10A	ENST00000524158.5	TSL:5	c.-301+5766C>T		intron	N/A	ENSP00000428884.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34338 AN: 151832 Hom.: 4120 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.226 AC: 34368 AN: 151950 Hom.: 4125 Cov.: 31 AF XY: 0.229 AC XY: 17027 AN XY: 74244

African (AFR) AF: 0.157 AC: 6523 AN: 41446

American (AMR) AF: 0.324 AC: 4948 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 927 AN: 3466

East Asian (EAS) AF: 0.298 AC: 1534 AN: 5150

South Asian (SAS) AF: 0.368 AC: 1767 AN: 4808

European-Finnish (FIN) AF: 0.205 AC: 2164 AN: 10556

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15678 AN: 67954

Other (OTH) AF: 0.243 AC: 512 AN: 2104

Alfa AF: 0.228 Hom.: 6210

Bravo AF: 0.230

Asia WGS AF: 0.325 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.31
PhyloP100		0.061
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: rs4872088; hg19: chr8-23076180;