Variant chr1-7938903-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001561.6(TNFRSF9):c.101-75A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.966 in 1,013,220 control chromosomes in the GnomAD database, including 472,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.97 ( 72084 hom., cov: 33)

Exomes 𝑓: 0.96 ( 400647 hom. )

Consequence

TNFRSF9
NM_001561.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.290

Variant links:

Genes affected

TNFRSF9 (HGNC:11924): (TNF receptor superfamily member 9) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contributes to the clonal expansion, survival, and development of T cells. It can also induce proliferation in peripheral monocytes, enhance T cell apoptosis induced by TCR/CD3 triggered activation, and regulate CD28 co-stimulation to promote Th1 cell responses. The expression of this receptor is induced by lymphocyte activation. TRAF adaptor proteins have been shown to bind to this receptor and transduce the signals leading to activation of NF-kappaB. [provided by RefSeq, Jul 2008]

TNFRSF9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 1-7938903-T-G is Benign according to our data. Variant chr1-7938903-T-G is described in ClinVar as [Benign]. Clinvar id is 2688134.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
TNFRSF9	NM_001561.6 linkuse as main transcript	c.101-75A>C	intron_variant	ENST00000377507.8
TNFRSF9	XM_006710618.4 linkuse as main transcript	c.101-75A>C	intron_variant
TNFRSF9	XM_047419672.1 linkuse as main transcript	c.101-75A>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF9	ENST00000377507.8 linkuse as main transcript	c.101-75A>C		intron_variant		1	NM_001561.6	P1
TNFRSF9	ENST00000674210.1 linkuse as main transcript	c.101-75A>C		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.972

AC:

148033

AN:

152228

Hom.:

72024

Cov.:

show subpopulations

Gnomad AFR

AF:

0.994

Gnomad AMI

AF:

0.995

Gnomad AMR

AF:

0.985

Gnomad ASJ

AF:

0.969

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.991

Gnomad FIN

AF:

0.942

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

0.958

Gnomad OTH

AF:

0.977

GnomAD4 exome

AF:

0.965

AC:

830397

AN:

860874

Hom.:

400647

AF XY:

0.965

AC XY:

425073

AN XY:

440396

show subpopulations

Gnomad4 AFR exome

AF:

0.994

Gnomad4 AMR exome

AF:

0.990

Gnomad4 ASJ exome

AF:

0.972

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.988

Gnomad4 FIN exome

AF:

0.940

Gnomad4 NFE exome

AF:

0.959

Gnomad4 OTH exome

AF:

0.967

GnomAD4 genome

AF:

0.972

AC:

148152

AN:

152346

Hom.:

72084

Cov.:

AF XY:

0.973

AC XY:

72469

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.994

Gnomad4 AMR

AF:

0.985

Gnomad4 ASJ

AF:

0.969

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.991

Gnomad4 FIN

AF:

0.942

Gnomad4 NFE

AF:

0.958

Gnomad4 OTH

AF:

0.977

Alfa

AF:

0.963

Hom.:

36107

Bravo

AF:

0.977

Asia WGS

AF:

0.996

AC:

3464

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 47% of patients studied by a panel of primary immunodeficiencies. Number of patients: 45. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

8.5

DANN

Benign

0.22

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over