1-7920936-T-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001561.6(TNFRSF9):c.680-13A>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,519,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: TNFRSF9 NM_001561.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.851

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-7920936-T-A is Benign according to our data. Variant chr1-7920936-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1610364.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF9	NM_001561.6	c.680-13A>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000377507.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF9	ENST00000377507.8	c.680-13A>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001561.6	P1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 151984 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000115 AC: 157 AN: 1367648 Hom.: 0 Cov.: 26 AF XY: 0.000115 AC XY: 79 AN XY: 684364

Gnomad4 AFR exome AF: 0.000160

Gnomad4 AMR exome AF: 0.000495

Gnomad4 ASJ exome AF: 0.000120

Gnomad4 EAS exome AF: 0.000129

Gnomad4 SAS exome AF: 0.0000607

Gnomad4 FIN exome AF: 0.000133

Gnomad4 NFE exome AF: 0.000104

Gnomad4 OTH exome AF: 0.0000527

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 151984 Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3 AN XY: 74246

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000478

Bravo AF: 0.0000642

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.043
Dann	Benign	0.30

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: rs778402646; hg19: chr1-7980996; COSMIC: COSV66349332; COSMIC: COSV66349332;