rs7030574

Variant names:

• chr9-114805769-C-A
• rs7030574
• NM_005118.4:c.210+34G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-114805769-C-A
• chr9-114805769-C-T

Variant summary

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

The NM_005118.4(TNFSF15):​c.210+34G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,599,906 control chromosomes in the GnomAD database, including 184,590 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 0.40 (13709 hom., cov: 32)
  • Exomes 𝑓: 0.48 (170881 hom.)
• Consequence: TNFSF15 NM_005118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 12 publications found

Genes affected

TNFSF15 (HGNC:11931): (TNF superfamily member 15) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is abundantly expressed in endothelial cells, but is not expressed in either B or T cells. The expression of this protein is inducible by TNF and IL-1 alpha. This cytokine is a ligand for receptor TNFRSF25 and decoy receptor TNFRSF21/DR6. It can activate NF-kappaB and MAP kinases, and acts as an autocrine factor to induce apoptosis in endothelial cells. This cytokine is also found to inhibit endothelial cell proliferation, and thus may function as an angiogenesis inhibitor. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF15	NM_005118.4	c.210+34G>T		intron_variant	Intron 1 of 3	ENST00000374045.5	NP_005109.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF15	ENST00000374045.5	c.210+34G>T		intron_variant	Intron 1 of 3	1	NM_005118.4	ENSP00000363157.3

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61384 AN: 151978 Hom.: 13709 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.0617

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.421

GnomAD2 exomes AF: 0.422 AC: 102816 AN: 243692 AF XY: 0.435

Gnomad AFR exome AF: 0.258

Gnomad AMR exome AF: 0.303

Gnomad ASJ exome AF: 0.575

Gnomad EAS exome AF: 0.0638

Gnomad FIN exome AF: 0.489

Gnomad NFE exome AF: 0.505

Gnomad OTH exome AF: 0.456

GnomAD4 exome AF: 0.477 AC: 690500 AN: 1447810 Hom.: 170881 Cov.: 30 AF XY: 0.479 AC XY: 344290 AN XY: 719316

African (AFR) AF: 0.251 AC: 8332 AN: 33188

American (AMR) AF: 0.307 AC: 13632 AN: 44336

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 14898 AN: 25878

East Asian (EAS) AF: 0.0474 AC: 1868 AN: 39434

South Asian (SAS) AF: 0.459 AC: 39362 AN: 85772

European-Finnish (FIN) AF: 0.489 AC: 25831 AN: 52854

Middle Eastern (MID) AF: 0.510 AC: 2183 AN: 4282

European-Non Finnish (NFE) AF: 0.505 AC: 556622 AN: 1102314

Other (OTH) AF: 0.465 AC: 27772 AN: 59752

GnomAD4 genome AF: 0.404 AC: 61394 AN: 152096 Hom.: 13709 Cov.: 32 AF XY: 0.400 AC XY: 29761 AN XY: 74358

African (AFR) AF: 0.264 AC: 10964 AN: 41502

American (AMR) AF: 0.371 AC: 5667 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1981 AN: 3470

East Asian (EAS) AF: 0.0614 AC: 318 AN: 5178

South Asian (SAS) AF: 0.444 AC: 2142 AN: 4824

European-Finnish (FIN) AF: 0.486 AC: 5130 AN: 10546

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33892 AN: 67968

Other (OTH) AF: 0.422 AC: 889 AN: 2108

Alfa AF: 0.431 Hom.: 4520

Bravo AF: 0.385

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.46
PhyloP100		0.093
PromoterAI		0.035	Neutral
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: rs7030574; hg19: chr9-117568049; COSMIC: COSV65011689;