1-2559632-C-G

Variant names:

• chr1-2559632-C-G
• rs143696469
• NM_003820.4:c.305-191C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003820.4(TNFRSF14):​c.305-191C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,534,812 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0029 (6 hom.)
• Consequence: TNFRSF14 NM_003820.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.80
• Publications: 2 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

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.305-191C>G		intron	N/A	NP_003811.2
	TNFRSF14	NM_001297605.2		c.305-191C>G		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.305-191C>G		intron	N/A	ENSP00000347948.4
	TNFRSF14	ENST00000475523.5	TSL:1	n.351C>G		non_coding_transcript_exon	Exon 2 of 6
	TNFRSF14	ENST00000860787.1		c.378C>G	p.Ala126Ala	synonymous	Exon 4 of 8	ENSP00000530846.1

Frequencies

GnomAD3 genomes AF: 0.00173 AC: 263 AN: 152246 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00235

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00275

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00145 AC: 197 AN: 135582 AF XY: 0.00149

Gnomad AFR exome AF: 0.000917

Gnomad AMR exome AF: 0.000735

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000368

Gnomad NFE exome AF: 0.00256

Gnomad OTH exome AF: 0.00334

GnomAD4 exome AF: 0.00289 AC: 3993 AN: 1382448 Hom.: 6 Cov.: 97 AF XY: 0.00282 AC XY: 1923 AN XY: 682164

African (AFR) AF: 0.000443 AC: 14 AN: 31588

American (AMR) AF: 0.000869 AC: 31 AN: 35678

Ashkenazi Jewish (ASJ) AF: 0.0000397 AC: 1 AN: 25170

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35704

South Asian (SAS) AF: 0.00102 AC: 80 AN: 78392

European-Finnish (FIN) AF: 0.000207 AC: 7 AN: 33788

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5694

European-Non Finnish (NFE) AF: 0.00347 AC: 3747 AN: 1078558

Other (OTH) AF: 0.00192 AC: 111 AN: 57876

GnomAD4 genome AF: 0.00173 AC: 263 AN: 152364 Hom.: 0 Cov.: 34 AF XY: 0.00153 AC XY: 114 AN XY: 74504

African (AFR) AF: 0.000745 AC: 31 AN: 41588

American (AMR) AF: 0.00235 AC: 36 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00275 AC: 187 AN: 68030

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000324 Hom.: 0

Bravo AF: 0.00214

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	-0.90
CADD	Benign	0.51
DANN	Benign	0.45
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

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: rs143696469; hg19: chr1-2491071;