8-23143612-A-T

Variant names:

• chr8-23143612-A-T
• rs6557618
• NM_003840.5:c.954+838T>A

Variant summary

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

The NM_003840.5(TNFRSF10D):​c.954+838T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 152,056 control chromosomes in the GnomAD database, including 48,079 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 0.79 (48079 hom., cov: 30)
• Consequence: TNFRSF10D NM_003840.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• Publications: 8 publications found

Genes affected

TNFRSF10D (HGNC:11907): (TNF receptor superfamily member 10d) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains an extracellular TRAIL-binding domain, a transmembrane domain, and a truncated cytoplamic death domain. This receptor does not induce apoptosis, and has been shown to play an inhibitory role in TRAIL-induced cell apoptosis. [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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10D	NM_003840.5	c.954+838T>A		intron_variant	Intron 7 of 8	ENST00000312584.4	NP_003831.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10D	ENST00000312584.4	c.954+838T>A		intron_variant	Intron 7 of 8	1	NM_003840.5	ENSP00000310263.3

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119397 AN: 151938 Hom.: 48006 Cov.: 30

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.786 AC: 119529 AN: 152056 Hom.: 48079 Cov.: 30 AF XY: 0.787 AC XY: 58478 AN XY: 74328

African (AFR) AF: 0.946 AC: 39276 AN: 41522

American (AMR) AF: 0.815 AC: 12441 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2238 AN: 3466

East Asian (EAS) AF: 0.925 AC: 4764 AN: 5152

South Asian (SAS) AF: 0.873 AC: 4204 AN: 4816

European-Finnish (FIN) AF: 0.661 AC: 6986 AN: 10564

Middle Eastern (MID) AF: 0.726 AC: 212 AN: 292

European-Non Finnish (NFE) AF: 0.694 AC: 47159 AN: 67968

Other (OTH) AF: 0.778 AC: 1639 AN: 2108

Alfa AF: 0.718 Hom.: 21950

Bravo AF: 0.804

Asia WGS AF: 0.904 AC: 3143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.30
DANN	Benign	0.53
PhyloP100		-0.39
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: rs6557618; hg19: chr8-23001125;