rs587777984

Variant names:

• chr1-2559347-C-T
• rs535767072
• NM_003820.4:c.305-476C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-2559347-C-T
• chrNT_187515.1-110537-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003820.4(TNFRSF14):​c.305-476C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000316 in 1,374,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00033 (0 hom.)
• Consequence: TNFRSF14 NM_003820.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.41
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003820.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF14	NM_003820.4	MANE Select	c.305-476C>T		intron	N/A	NP_003811.2
	TNFRSF14	NM_001297605.2		c.305-476C>T		intron	N/A	NP_001284534.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF14	ENST00000355716.5	TSL:1 MANE Select	c.305-476C>T		intron	N/A	ENSP00000347948.4
	TNFRSF14	ENST00000475523.5	TSL:1	n.71-5C>T		splice_region intron	N/A
	TNFRSF14	ENST00000860787.1		c.305-212C>T		intron	N/A	ENSP00000530846.1

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000127 AC: 17 AN: 133986 AF XY: 0.000110

Gnomad AFR exome AF: 0.000155

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000187

Gnomad NFE exome AF: 0.000285

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000328 AC: 401 AN: 1222674 Hom.: 0 Cov.: 30 AF XY: 0.000330 AC XY: 197 AN XY: 597278

African (AFR) AF: 0.000105 AC: 3 AN: 28498

American (AMR) AF: 0.00 AC: 0 AN: 30820

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21172

East Asian (EAS) AF: 0.00 AC: 0 AN: 24324

South Asian (SAS) AF: 0.00 AC: 0 AN: 76872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4918

European-Non Finnish (NFE) AF: 0.000394 AC: 384 AN: 974178

Other (OTH) AF: 0.000288 AC: 14 AN: 48580

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152306 Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12 AN XY: 74478

African (AFR) AF: 0.0000481 AC: 2 AN: 41574

American (AMR) AF: 0.000196 AC: 3 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000204

ClinVar

ClinVar submissions as Germline

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.39
PhyloP100		-1.4
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

Other links and lift over

dbSNP: rs535767072; hg19: chr1-2490786;