rs11573975

Variant names:

• chr1-2559013-C-T
• rs11573975
• NM_003820.4:c.304+545C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-2559013-C-T
• chr1-2559013-C-A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_003820.4(TNFRSF14):​c.304+545C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,367,694 control chromosomes in the GnomAD database, including 26 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 0.0081 (12 hom., cov: 34)
  • Exomes 𝑓: 0.00082 (14 hom.)
• Consequence: TNFRSF14 NM_003820.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.87
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00807 (1230/152348) while in subpopulation AFR AF = 0.0286 (1187/41570). AF 95% confidence interval is 0.0272. There are 12 homozygotes in GnomAd4. There are 553 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 12 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.304+545C>T		intron	N/A	NP_003811.2
	TNFRSF14	NM_001297605.2		c.304+545C>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.304+545C>T		intron	N/A	ENSP00000347948.4	Q92956-1
	TNFRSF14	ENST00000475523.5	TSL:1	n.71-339C>T		intron	N/A
	TNFRSF14	ENST00000860787.1		c.304+545C>T		intron	N/A	ENSP00000530846.1

Frequencies

GnomAD3 genomes AF: 0.00807 AC: 1229 AN: 152230 Hom.: 12 Cov.: 34

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00163

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: 0.000103

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00170 AC: 224 AN: 131510 AF XY: 0.00114

Gnomad AFR exome AF: 0.0292

Gnomad AMR exome AF: 0.00123

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000398

Gnomad OTH exome AF: 0.00122

GnomAD4 exome AF: 0.000820 AC: 997 AN: 1215346 Hom.: 14 Cov.: 30 AF XY: 0.000731 AC XY: 434 AN XY: 593878

African (AFR) AF: 0.0293 AC: 825 AN: 28110

American (AMR) AF: 0.00127 AC: 39 AN: 30652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20878

East Asian (EAS) AF: 0.00 AC: 0 AN: 23890

South Asian (SAS) AF: 0.000156 AC: 12 AN: 76876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12860

Middle Eastern (MID) AF: 0.000617 AC: 3 AN: 4862

European-Non Finnish (NFE) AF: 0.0000351 AC: 34 AN: 969136

Other (OTH) AF: 0.00175 AC: 84 AN: 48082

GnomAD4 genome AF: 0.00807 AC: 1230 AN: 152348 Hom.: 12 Cov.: 34 AF XY: 0.00742 AC XY: 553 AN XY: 74500

African (AFR) AF: 0.0286 AC: 1187 AN: 41570

American (AMR) AF: 0.00163 AC: 25 AN: 15312

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

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

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68042

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.000289 Hom.: 1

Bravo AF: 0.00947

Asia WGS AF: 0.00115 AC: 5 AN: 3478

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	-0.90
CADD	Benign	1.7
DANN	Benign	0.56
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11573975; hg19: chr1-2490452; COSMIC: COSV63187190; COSMIC: COSV63187190;