ENST00000475523.5:n.145T>A

Variant names:

• chr1-2559426-T-A
• rs587777987
• ENST00000475523.5:n.145T>A

Variant summary

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

The ENST00000475523.5(TNFRSF14):​n.145T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000242 in 1,237,118 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: 0.0000024 (0 hom.)
• Consequence: TNFRSF14 ENST00000475523.5 non_coding_transcript_exon
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.37
• 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=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000475523.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF14	NM_003820.4	MANE Select	c.305-397T>A		intron	N/A	NP_003811.2
	TNFRSF14	NM_001297605.2		c.305-397T>A		intron	N/A	NP_001284534.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF14	ENST00000475523.5	TSL:1	n.145T>A		non_coding_transcript_exon	Exon 2 of 6
	TNFRSF14	ENST00000355716.5	TSL:1 MANE Select	c.305-397T>A		intron	N/A	ENSP00000347948.4
	TNFRSF14	ENST00000463471.6	TSL:2	n.1356T>A		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000242 AC: 3 AN: 1237118 Hom.: 0 Cov.: 30 AF XY: 0.00000331 AC XY: 2 AN XY: 605012

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28726

American (AMR) AF: 0.00 AC: 0 AN: 31172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21548

East Asian (EAS) AF: 0.00 AC: 0 AN: 24470

South Asian (SAS) AF: 0.00 AC: 0 AN: 77072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4994

European-Non Finnish (NFE) AF: 0.00000305 AC: 3 AN: 984586

Other (OTH) AF: 0.00 AC: 0 AN: 49356

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00131091), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.45
DANN	Benign	0.73
PhyloP100		-1.4

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: rs587777987; hg19: chr1-2490865;