1-7920925-TA-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_001561.6(TNFRSF9):c.680-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,500,608 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (0 hom.)
• Consequence: TNFRSF9 NM_001561.6 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.222

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
• BP6: Variant 1-7920925-TA-T is Benign according to our data. Variant chr1-7920925-TA-T is described in ClinVar as [Benign]. Clinvar id is 1566533.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00151 (2038/1350334) while in subpopulation AMR AF= 0.00214 (83/38822). AF 95% confidence interval is 0.00177. There are 0 homozygotes in gnomad4_exome. There are 983 alleles in male gnomad4_exome subpopulation. Median coverage is 28. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF9	NM_001561.6	c.680-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000377507.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF9	ENST00000377507.8	c.680-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001561.6	P1

Frequencies

GnomAD3 genomes AF: 0.0000399 AC: 6 AN: 150274 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000985

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000593

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00151 AC: 2038 AN: 1350334 Hom.: 0 Cov.: 28 AF XY: 0.00146 AC XY: 983 AN XY: 671224

Gnomad4 AFR exome AF: 0.00155

Gnomad4 AMR exome AF: 0.00214

Gnomad4 ASJ exome AF: 0.00120

Gnomad4 EAS exome AF: 0.00106

Gnomad4 SAS exome AF: 0.00134

Gnomad4 FIN exome AF: 0.000588

Gnomad4 NFE exome AF: 0.00156

Gnomad4 OTH exome AF: 0.00167

GnomAD4 genome AF: 0.0000399 AC: 6 AN: 150274 Hom.: 0 Cov.: 31 AF XY: 0.0000410 AC XY: 3 AN XY: 73228

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000985

Gnomad4 NFE AF: 0.0000593

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00825 Hom.: 0

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

Mar 12, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs767796238; hg19: chr1-7980985;