chr1-7922756-G-A

Variant names:

• chr1-7922756-G-A
• rs17229081
• NM_001561.6:c.680-1833C>T

Variant summary

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

The NM_001561.6(TNFRSF9):​c.680-1833C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 151,610 control chromosomes in the GnomAD database, including 1,603 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 0.13 (1603 hom., cov: 30)
• Consequence: TNFRSF9 NM_001561.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF9	NM_001561.6	c.680-1833C>T		intron_variant	Intron 7 of 7	ENST00000377507.8	NP_001552.2
TNFRSF9	XM_006710618.4	c.680-735C>T		intron_variant	Intron 7 of 7		XP_006710681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF9	ENST00000377507.8	c.680-1833C>T		intron_variant	Intron 7 of 7	1	NM_001561.6	ENSP00000366729.3
TNFRSF9	ENST00000474475.1	c.224-735C>T		intron_variant	Intron 2 of 2	3		ENSP00000465272.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19818 AN: 151492 Hom.: 1597 Cov.: 30

Gnomad AFR AF: 0.0705

Gnomad AMI AF: 0.0639

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0856

Gnomad EAS AF: 0.0614

Gnomad SAS AF: 0.0919

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.0577

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.131 AC: 19831 AN: 151610 Hom.: 1603 Cov.: 30 AF XY: 0.132 AC XY: 9780 AN XY: 74060

African (AFR) AF: 0.0707 AC: 2927 AN: 41404

American (AMR) AF: 0.103 AC: 1574 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0856 AC: 297 AN: 3468

East Asian (EAS) AF: 0.0613 AC: 312 AN: 5086

South Asian (SAS) AF: 0.0916 AC: 440 AN: 4806

European-Finnish (FIN) AF: 0.274 AC: 2867 AN: 10466

Middle Eastern (MID) AF: 0.0655 AC: 19 AN: 290

European-Non Finnish (NFE) AF: 0.164 AC: 11099 AN: 67840

Other (OTH) AF: 0.113 AC: 238 AN: 2104

Alfa AF: 0.0849 Hom.: 129

Bravo AF: 0.117

Asia WGS AF: 0.0740 AC: 258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.27
PhyloP100		0.34
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: rs17229081; hg19: chr1-7982816;