chr1-2559622-G-T

Variant names:

• chr1-2559622-G-T
• rs112070015
• ENST00000475523.5:n.341G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000475523.5(TNFRSF14):​n.341G>T 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 0.000000724 in 1,382,000 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: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TNFRSF14 ENST00000475523.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.305-201G>T		intron	N/A	NP_003811.2
	TNFRSF14	NM_001297605.2		c.305-201G>T		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.341G>T		non_coding_transcript_exon	Exon 2 of 6
	TNFRSF14	ENST00000355716.5	TSL:1 MANE Select	c.305-201G>T		intron	N/A	ENSP00000347948.4
	TNFRSF14	ENST00000463471.6	TSL:2	n.1552G>T		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1382000 Hom.: 0 Cov.: 96 AF XY: 0.00000147 AC XY: 1 AN XY: 681922

African (AFR) AF: 0.00 AC: 0 AN: 31574

American (AMR) AF: 0.00 AC: 0 AN: 35666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25160

East Asian (EAS) AF: 0.00 AC: 0 AN: 35686

South Asian (SAS) AF: 0.00 AC: 0 AN: 78380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078294

Other (OTH) AF: 0.0000173 AC: 1 AN: 57838

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.32
DANN	Benign	0.43
PhyloP100		-1.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: 38

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs112070015; hg19: chr1-2491061;