1-2559361-G-T

Variant names:

• chr1-2559361-G-T
• rs587777985
• NM_003820.4:c.305-462G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003820.4(TNFRSF14):​c.305-462G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000409 in 1,223,152 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TNFRSF14 NM_003820.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -3.01
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

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.305-462G>T		intron	N/A	NP_003811.2
	TNFRSF14	NM_001297605.2		c.305-462G>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.305-462G>T		intron	N/A	ENSP00000347948.4	Q92956-1
	TNFRSF14	ENST00000475523.5	TSL:1	n.80G>T		non_coding_transcript_exon	Exon 2 of 6
	TNFRSF14	ENST00000860787.1		c.305-198G>T		intron	N/A	ENSP00000530846.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000744 AC: 1 AN: 134380 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000409

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000409 AC: 5 AN: 1223152 Hom.: 0 Cov.: 30 AF XY: 0.00000669 AC XY: 4 AN XY: 597586

African (AFR) AF: 0.00 AC: 0 AN: 28512

American (AMR) AF: 0.0000324 AC: 1 AN: 30864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21230

East Asian (EAS) AF: 0.0000411 AC: 1 AN: 24360

South Asian (SAS) AF: 0.00 AC: 0 AN: 76944

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4924

European-Non Finnish (NFE) AF: 0.00000308 AC: 3 AN: 974388

Other (OTH) AF: 0.00 AC: 0 AN: 48608

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

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	-0.94
CADD	Benign	0.58
DANN	Benign	0.37
PhyloP100		-3.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs587777985; hg19: chr1-2490800;