Variant 1-7936574-A-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.413+1116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,288 control chromosomes in the GnomAD database, including 45,955 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.77 ( 45941 hom., cov: 33)

Exomes 𝑓: 0.80 ( 14 hom. )

Consequence

TNFRSF9
NM_001561.6 intron

Scores

Splicing: ADA: 0.00001597

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.00

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=-0.99).

BP6

Variant 1-7936574-A-G is Benign according to our data. Variant chr1-7936574-A-G is described in ClinVar as [Benign]. Clinvar id is 2688454.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
TNFRSF9	NM_001561.6 linkuse as main transcript	c.413+1116T>C	intron_variant	ENST00000377507.8
TNFRSF9	XM_006710618.4 linkuse as main transcript	c.413+1116T>C	intron_variant
TNFRSF9	XM_047419672.1 linkuse as main transcript	c.413+1116T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF9	ENST00000377507.8 linkuse as main transcript	c.413+1116T>C		intron_variant		1	NM_001561.6	P1
TNFRSF9	ENST00000492571.1 linkuse as main transcript	c.180-11T>C		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.767

AC:

116630

AN:

152126

Hom.:

45875

Cov.:

show subpopulations

Gnomad AFR

AF:

0.924

Gnomad AMI

AF:

0.693

Gnomad AMR

AF:

0.791

Gnomad ASJ

AF:

0.598

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.783

Gnomad FIN

AF:

0.714

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.665

Gnomad OTH

AF:

0.748

GnomAD3 exomes

AF:

1.00

AC:

AN:

Hom.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

Gnomad NFE exome

AF:

1.00

GnomAD4 exome

AF:

0.795

AC:

AN:

Hom.:

Cov.:

AF XY:

0.813

AC XY:

AN XY:

show subpopulations

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.625

Gnomad4 NFE exome

AF:

0.773

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.767

AC:

116756

AN:

152244

Hom.:

45941

Cov.:

AF XY:

0.770

AC XY:

57339

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.924

Gnomad4 AMR

AF:

0.791

Gnomad4 ASJ

AF:

0.598

Gnomad4 EAS

AF:

0.998

Gnomad4 SAS

AF:

0.783

Gnomad4 FIN

AF:

0.714

Gnomad4 NFE

AF:

0.665

Gnomad4 OTH

AF:

0.753

Alfa

AF:

0.723

Hom.:

5170

Bravo

AF:

0.781

Asia WGS

AF:

0.900

AC:

3132

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 94% of patients studied by a panel of primary immunodeficiencies. Number of patients: 83. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

3.8

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.020

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