1-1211405-G-C

Position:

• chr1-1211405-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003327.4(TNFRSF4):​c.*150C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 702,290 control chromosomes in the GnomAD database, including 426 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 0.019 (55 hom., cov: 33)
  • Exomes 𝑓: 0.024 (371 hom.)
• Consequence: TNFRSF4 NM_003327.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41

Genes affected

TNFRSF4 (HGNC:11918): (TNF receptor superfamily member 4) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor has been shown to activate NF-kappaB through its interaction with adaptor proteins TRAF2 and TRAF5. Knockout studies in mice suggested that this receptor promotes the expression of apoptosis inhibitors BCL2 and BCL2lL1/BCL2-XL, and thus suppresses apoptosis. The knockout studies also suggested the roles of this receptor in CD4+ T cell response, as well as in T cell-dependent B cell proliferation and differentiation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF4	NM_003327.4	c.*150C>G		3_prime_UTR_variant	7/7	ENST00000379236.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF4	ENST00000379236.4	c.*150C>G		3_prime_UTR_variant	7/7	1	NM_003327.4	P1

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2899 AN: 152228 Hom.: 55 Cov.: 33

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0356

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0160

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.0239 AC: 13130 AN: 549944 Hom.: 371 Cov.: 8 AF XY: 0.0231 AC XY: 6409 AN XY: 276926

Gnomad4 AFR exome AF: 0.0128

Gnomad4 AMR exome AF: 0.0148

Gnomad4 ASJ exome AF: 0.00469

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.0117

Gnomad4 FIN exome AF: 0.0422

Gnomad4 NFE exome AF: 0.0174

Gnomad4 OTH exome AF: 0.0255

GnomAD4 genome AF: 0.0190 AC: 2899 AN: 152346 Hom.: 55 Cov.: 33 AF XY: 0.0197 AC XY: 1470 AN XY: 74502

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.0125

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.0124

Gnomad4 FIN AF: 0.0356

Gnomad4 NFE AF: 0.0160

Gnomad4 OTH AF: 0.0198

Alfa AF: 0.0185 Hom.: 1

Bravo AF: 0.0174

Asia WGS AF: 0.0610 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs2298209; hg19: chr1-1146785; COSMIC: COSV60774670; COSMIC: COSV60774670;