Menu
GeneBe

8-23147026-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_003840.5(TNFRSF10D):c.417T>C(p.Cys139=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,613,658 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0078 ( 24 hom., cov: 32)
Exomes 𝑓: 0.00079 ( 18 hom. )

Consequence

TNFRSF10D
NM_003840.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.295
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-23147026-A-G is Benign according to our data. Variant chr8-23147026-A-G is described in ClinVar as [Benign]. Clinvar id is 776295.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.295 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00777 (1179/151788) while in subpopulation AFR AF= 0.0274 (1130/41168). AF 95% confidence interval is 0.0261. There are 24 homozygotes in gnomad4. There are 558 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 24 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TNFRSF10DNM_003840.5 linkuse as main transcriptc.417T>C p.Cys139= synonymous_variant 4/9 ENST00000312584.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TNFRSF10DENST00000312584.4 linkuse as main transcriptc.417T>C p.Cys139= synonymous_variant 4/91 NM_003840.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00779
AC:
1181
AN:
151672
Hom.:
24
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0276
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00216
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000209
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00574
GnomAD3 exomes
AF:
0.00202
AC:
509
AN:
251480
Hom.:
10
AF XY:
0.00144
AC XY:
196
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.0281
Gnomad AMR exome
AF:
0.00130
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.000814
GnomAD4 exome
AF:
0.000794
AC:
1161
AN:
1461870
Hom.:
18
Cov.:
31
AF XY:
0.000677
AC XY:
492
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.0289
Gnomad4 AMR exome
AF:
0.00148
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.00167
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00777
AC:
1179
AN:
151788
Hom.:
24
Cov.:
32
AF XY:
0.00752
AC XY:
558
AN XY:
74230
show subpopulations
Gnomad4 AFR
AF:
0.0274
Gnomad4 AMR
AF:
0.00216
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000209
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00569
Alfa
AF:
0.00348
Hom.:
6
Bravo
AF:
0.00890
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 19, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
Cadd
Benign
3.4
Dann
Benign
0.44

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61736092; hg19: chr8-23004539; API