rs587777983

Variant names:

• chr1-2559170-T-C
• rs148507536
• NM_003820.4:c.305-653T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-2559170-T-C
• chrNT_187515.1-110360-T-C

Variant summary

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

The NM_003820.4(TNFRSF14):​c.305-653T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,366,842 control chromosomes in the GnomAD database, including 23 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 0.0026 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0036 (19 hom.)
• Consequence: TNFRSF14 NM_003820.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -2.83
• 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=-0.93).
• BS2: High Homozygotes in GnomAd4 at 4 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.305-653T>C		intron	N/A	NP_003811.2
	TNFRSF14	NM_001297605.2		c.305-653T>C		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.305-653T>C		intron	N/A	ENSP00000347948.4
	TNFRSF14	ENST00000475523.5	TSL:1	n.71-182T>C		intron	N/A
	TNFRSF14	ENST00000860787.1		c.305-389T>C		intron	N/A	ENSP00000530846.1

Frequencies

GnomAD3 genomes AF: 0.00264 AC: 401 AN: 152166 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.00584

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00400

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00321 AC: 425 AN: 132204 AF XY: 0.00388

Gnomad AFR exome AF: 0.000313

Gnomad AMR exome AF: 0.000618

Gnomad ASJ exome AF: 0.00443

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00378

Gnomad NFE exome AF: 0.00374

Gnomad OTH exome AF: 0.00270

GnomAD4 exome AF: 0.00362 AC: 4397 AN: 1214558 Hom.: 19 Cov.: 30 AF XY: 0.00376 AC XY: 2231 AN XY: 592664

African (AFR) AF: 0.000354 AC: 10 AN: 28232

American (AMR) AF: 0.000589 AC: 18 AN: 30558

Ashkenazi Jewish (ASJ) AF: 0.00426 AC: 89 AN: 20898

East Asian (EAS) AF: 0.00 AC: 0 AN: 24110

South Asian (SAS) AF: 0.00669 AC: 513 AN: 76644

European-Finnish (FIN) AF: 0.00288 AC: 37 AN: 12830

Middle Eastern (MID) AF: 0.00123 AC: 6 AN: 4886

European-Non Finnish (NFE) AF: 0.00368 AC: 3560 AN: 968304

Other (OTH) AF: 0.00341 AC: 164 AN: 48096

GnomAD4 genome AF: 0.00263 AC: 401 AN: 152284 Hom.: 4 Cov.: 33 AF XY: 0.00277 AC XY: 206 AN XY: 74458

African (AFR) AF: 0.000313 AC: 13 AN: 41566

American (AMR) AF: 0.000523 AC: 8 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4828

European-Finnish (FIN) AF: 0.00584 AC: 62 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00400 AC: 272 AN: 68008

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00470 Hom.: 1

Bravo AF: 0.00192

Asia WGS AF: 0.00115 AC: 4 AN: 3478

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	-0.93
CADD	Benign	0.29
DANN	Benign	0.38
PhyloP100		-2.8
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: rs148507536; hg19: chr1-2490609; COSMIC: COSV106502295;