8-23191695-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003844.4(TNFRSF10A):c.1406G>T(p.Ter469LeuextTer15) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000875 in 1,610,852 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00080 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00088 (3 hom.)
• Consequence: TNFRSF10A NM_003844.4 stop_lost
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.240

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.784305).
• BP6: Variant 8-23191695-C-A is Benign according to our data. Variant chr8-23191695-C-A is described in ClinVar as [Benign]. Clinvar id is 784502.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 121 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF10A	NM_003844.4	c.1406G>T	p.Ter469LeuextTer15	stop_lost	10/10	ENST00000221132.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF10A	ENST00000221132.8	c.1406G>T	p.Ter469LeuextTer15	stop_lost	10/10	1	NM_003844.4	P1
TNFRSF10A	ENST00000613472.1	c.932G>T	p.Ter311LeuextTer15	stop_lost	9/9	1

Frequencies

GnomAD3 genomes AF: 0.000796 AC: 121 AN: 152044 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00131 AC: 325 AN: 247736 Hom.: 2 AF XY: 0.00131 AC XY: 176 AN XY: 134030

Gnomad AFR exome AF: 0.000309

Gnomad AMR exome AF: 0.00134

Gnomad ASJ exome AF: 0.0148

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000330

Gnomad FIN exome AF: 0.0000937

Gnomad NFE exome AF: 0.00101

Gnomad OTH exome AF: 0.00216

GnomAD4 exome AF: 0.000883 AC: 1288 AN: 1458698 Hom.: 3 Cov.: 52 AF XY: 0.000912 AC XY: 662 AN XY: 725526

Gnomad4 AFR exome AF: 0.0000902

Gnomad4 AMR exome AF: 0.00135

Gnomad4 ASJ exome AF: 0.0144

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.0000564

Gnomad4 NFE exome AF: 0.000652

Gnomad4 OTH exome AF: 0.00184

GnomAD4 genome AF: 0.000795 AC: 121 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.000712 AC XY: 53 AN XY: 74394

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000882

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00166 Hom.: 1

Bravo AF: 0.000960

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00209 AC: 18

ExAC AF: 0.00119 AC: 145

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00202

EpiControl AF: 0.00154

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.41
Dann	Benign	0.72
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.018	N
MutationTaster	Benign	1.0	N
Vest4		0.16
GERP RS		-1.7

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: rs144773234; hg19: chr8-23049208;