ENST00000674210.1:c.-235+190G>A

Variant names:

• chr1-7942949-C-T
• rs17229038
• ENST00000674210.1:c.-235+190G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000674210.1(TNFRSF9):​c.-235+190G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 152,300 control chromosomes in the GnomAD database, including 69 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 0.025 (69 hom., cov: 31)
• Consequence: TNFRSF9 ENST00000674210.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 2 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

ENSG00000270330 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0251 (3826/152300) while in subpopulation NFE AF = 0.0357 (2428/68024). AF 95% confidence interval is 0.0345. There are 69 homozygotes in GnomAd4. There are 1895 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 69 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF9	ENST00000674210.1	c.-235+190G>A		intron_variant	Intron 1 of 4			ENSP00000501326.1
ENSG00000270330	ENST00000603760.1	n.*223C>T		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3824 AN: 152182 Hom.: 69 Cov.: 31

Gnomad AFR AF: 0.00681

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0233

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.0512

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0268

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

GnomAD4 genome AF: 0.0251 AC: 3826 AN: 152300 Hom.: 69 Cov.: 31 AF XY: 0.0254 AC XY: 1895 AN XY: 74486

African (AFR) AF: 0.00681 AC: 283 AN: 41562

American (AMR) AF: 0.0233 AC: 356 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00477 AC: 23 AN: 4822

European-Finnish (FIN) AF: 0.0512 AC: 544 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0357 AC: 2428 AN: 68024

Other (OTH) AF: 0.0265 AC: 56 AN: 2110

Alfa AF: 0.0284 Hom.: 9

Bravo AF: 0.0228

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.74
PhyloP100		-0.099
PromoterAI		-0.020	Neutral

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: rs17229038; hg19: chr1-8003009;