1-2559459-C-T

Position:

• chr1-2559459-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003820.4(TNFRSF14):​c.305-364C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,411,598 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (0 hom.)
• Consequence: TNFRSF14 NM_003820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

Genes affected

TNFRSF14 (HGNC:11912): (TNF receptor superfamily member 14) This gene encodes a member of the TNF (tumor necrosis factor) receptor superfamily. The encoded protein functions in signal transduction pathways that activate inflammatory and inhibitory T-cell immune response. It binds herpes simplex virus (HSV) viral envelope glycoprotein D (gD), mediating its entry into cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF14	NM_003820.4	c.305-364C>T		intron_variant		ENST00000355716.5	NP_003811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF14	ENST00000355716.5	c.305-364C>T		intron_variant		1	NM_003820.4	ENSP00000347948	P1

Frequencies

GnomAD3 genomes AF: 0.000323 AC: 49 AN: 151494 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00137

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.000382

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00151 AC: 1904 AN: 1259990 Hom.: 0 Cov.: 62 AF XY: 0.00146 AC XY: 901 AN XY: 617226

Gnomad4 AFR exome AF: 0.00282

Gnomad4 AMR exome AF: 0.000249

Gnomad4 ASJ exome AF: 0.000890

Gnomad4 EAS exome AF: 0.000641

Gnomad4 SAS exome AF: 0.000766

Gnomad4 FIN exome AF: 0.0000530

Gnomad4 NFE exome AF: 0.00165

Gnomad4 OTH exome AF: 0.00131

GnomAD4 genome AF: 0.000310 AC: 47 AN: 151608 Hom.: 0 Cov.: 32 AF XY: 0.000337 AC XY: 25 AN XY: 74084

Gnomad4 AFR AF: 0.000435

Gnomad4 AMR AF: 0.000197

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00137

Gnomad4 SAS AF: 0.00105

Gnomad4 FIN AF: 0.000382

Gnomad4 NFE AF: 0.000133

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2257763; hg19: chr1-2490898;