chr1-7921974-T-C

Position:

• chr1-7921974-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001561.6(TNFRSF9):​c.680-1051A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,176 control chromosomes in the GnomAD database, including 2,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (2435 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNFRSF9 NM_001561.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.17

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-7921974-T-C is Benign according to our data. Variant chr1-7921974-T-C is described in ClinVar as [Benign]. Clinvar id is 2688421.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF9	NM_001561.6	c.680-1051A>G		intron_variant		ENST00000377507.8	NP_001552.2
TNFRSF9	XM_006710618.4	c.*7A>G		3_prime_UTR_variant	8/8		XP_006710681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF9	ENST00000377507.8	c.680-1051A>G		intron_variant		1	NM_001561.6	ENSP00000366729.3
TNFRSF9	ENST00000474475	c.*7A>G		3_prime_UTR_variant	3/3	3		ENSP00000465272.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18270 AN: 152058 Hom.: 2424 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.0590

Gnomad FIN AF: 0.0139

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.106

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.120 AC: 18314 AN: 152176 Hom.: 2435 Cov.: 31 AF XY: 0.123 AC XY: 9135 AN XY: 74424

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.0524

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.0591

Gnomad4 FIN AF: 0.0139

Gnomad4 NFE AF: 0.0220

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0556 Hom.: 860

Bravo AF: 0.148

Asia WGS AF: 0.308 AC: 1067 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 48% of patients studied by a panel of primary immunodeficiencies. Number of patients: 42. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs161827; hg19: chr1-7982034;