1-7939542-C-T

Variant names:

• chr1-7939542-C-T
• rs161811
• NM_001561.6:c.100+353G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001561.6(TNFRSF9):​c.100+353G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0902 in 152,130 control chromosomes in the GnomAD database, including 1,585 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.090 (1585 hom., cov: 32)
• Consequence: TNFRSF9 NM_001561.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.16
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 109 with lymphoproliferation

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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 rank	MANE	Protein	UniProt
TNFRSF9	NM_001561.6	c.100+353G>A		intron_variant	Intron 2 of 7	ENST00000377507.8	NP_001552.2
TNFRSF9	XM_006710618.4	c.100+353G>A		intron_variant	Intron 2 of 7		XP_006710681.1
TNFRSF9	XM_047419672.1	c.100+353G>A		intron_variant	Intron 2 of 7		XP_047275628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF9	ENST00000377507.8	c.100+353G>A		intron_variant	Intron 2 of 7	1	NM_001561.6	ENSP00000366729.3
TNFRSF9	ENST00000674210.1	c.100+353G>A		intron_variant	Intron 3 of 4			ENSP00000501326.1

Frequencies

GnomAD3 genomes AF: 0.0901 AC: 13697 AN: 152014 Hom.: 1579 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.0570

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0837

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0902 AC: 13723 AN: 152130 Hom.: 1585 Cov.: 32 AF XY: 0.0937 AC XY: 6971 AN XY: 74376

African (AFR) AF: 0.132 AC: 5460 AN: 41500

American (AMR) AF: 0.220 AC: 3359 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0605 AC: 210 AN: 3472

East Asian (EAS) AF: 0.514 AC: 2653 AN: 5160

South Asian (SAS) AF: 0.0570 AC: 275 AN: 4824

European-Finnish (FIN) AF: 0.0130 AC: 138 AN: 10598

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0212 AC: 1439 AN: 68004

Other (OTH) AF: 0.0851 AC: 180 AN: 2114

Alfa AF: 0.0509 Hom.: 3171

Bravo AF: 0.115

Asia WGS AF: 0.287 AC: 995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.066
DANN	Benign	0.66
PhyloP100		-4.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs161811; hg19: chr1-7999602;