8-23197125-C-T

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.1087+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00044 in 1,614,138 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: TNFRSF10A NM_003844.4 splice_region, intron
• Scores: Splicing: ADA: 0.00005506
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.972

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_noAF=-0.81).
• BP6: Variant 8-23197125-C-T is Benign according to our data. Variant chr8-23197125-C-T is described in ClinVar as [Benign]. Clinvar id is 783519.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 373 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF10A	NM_003844.4	c.1087+7G>A		splice_region_variant, intron_variant		ENST00000221132.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF10A	ENST00000221132.8	c.1087+7G>A		splice_region_variant, intron_variant		1	NM_003844.4	P1
TNFRSF10A	ENST00000613472.1	c.613+7G>A		splice_region_variant, intron_variant		1
TNFRSF10A	ENST00000519862.1	n.142+7G>A		splice_region_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00245 AC: 373 AN: 152196 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00859

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.000652 AC: 164 AN: 251496 Hom.: 2 AF XY: 0.000567 AC XY: 77 AN XY: 135922

Gnomad AFR exome AF: 0.00898

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000231 AC: 337 AN: 1461824 Hom.: 0 Cov.: 31 AF XY: 0.000206 AC XY: 150 AN XY: 727214

Gnomad4 AFR exome AF: 0.00812

Gnomad4 AMR exome AF: 0.000604

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.000546

GnomAD4 genome AF: 0.00246 AC: 374 AN: 152314 Hom.: 3 Cov.: 32 AF XY: 0.00240 AC XY: 179 AN XY: 74488

Gnomad4 AFR AF: 0.00859

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00179 Hom.: 0

Bravo AF: 0.00270

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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

Jul 18, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.86
Dann	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000055
dbscSNV1_RF	Benign	0.0020
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: rs75047372; hg19: chr8-23054638;