rs587777997

Variant names:

• chr1-2559766-C-T
• rs2234161
• NM_003820.4:c.305-57C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-2559766-C-T
• chrNT_187515.1-110956-C-T
• chr1-2559766-C-G
• chrNT_187515.1-110956-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003820.4(TNFRSF14):​c.305-57C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,558,776 control chromosomes in the GnomAD database, including 214,939 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 0.58 (26835 hom., cov: 33)
  • Exomes 𝑓: 0.51 (188104 hom.)
• Consequence: TNFRSF14 NM_003820.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.93
• Publications: 27 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

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.305-57C>T		intron	N/A	NP_003811.2
	TNFRSF14	NM_001297605.2		c.305-57C>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.305-57C>T		intron	N/A	ENSP00000347948.4
	TNFRSF14	ENST00000475523.5	TSL:1	n.485C>T		non_coding_transcript_exon	Exon 2 of 6
	TNFRSF14	ENST00000860787.1		c.512C>T	p.Pro171Leu	missense	Exon 4 of 8	ENSP00000530846.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88150 AN: 151980 Hom.: 26787 Cov.: 33

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.548

GnomAD2 exomes AF: 0.553 AC: 93669 AN: 169440 AF XY: 0.553

Gnomad AFR exome AF: 0.797

Gnomad AMR exome AF: 0.548

Gnomad ASJ exome AF: 0.460

Gnomad EAS exome AF: 0.554

Gnomad FIN exome AF: 0.509

Gnomad NFE exome AF: 0.503

Gnomad OTH exome AF: 0.524

GnomAD4 exome AF: 0.513 AC: 721736 AN: 1406678 Hom.: 188104 Cov.: 95 AF XY: 0.516 AC XY: 359477 AN XY: 696134

African (AFR) AF: 0.785 AC: 25607 AN: 32620

American (AMR) AF: 0.544 AC: 20679 AN: 37982

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 11772 AN: 25346

East Asian (EAS) AF: 0.524 AC: 19460 AN: 37160

South Asian (SAS) AF: 0.640 AC: 51806 AN: 80994

European-Finnish (FIN) AF: 0.492 AC: 19657 AN: 39960

Middle Eastern (MID) AF: 0.548 AC: 3132 AN: 5712

European-Non Finnish (NFE) AF: 0.495 AC: 538438 AN: 1088300

Other (OTH) AF: 0.532 AC: 31185 AN: 58604

GnomAD4 genome AF: 0.580 AC: 88252 AN: 152098 Hom.: 26835 Cov.: 33 AF XY: 0.581 AC XY: 43204 AN XY: 74354

African (AFR) AF: 0.768 AC: 31912 AN: 41526

American (AMR) AF: 0.564 AC: 8620 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1589 AN: 3472

East Asian (EAS) AF: 0.543 AC: 2795 AN: 5150

South Asian (SAS) AF: 0.652 AC: 3145 AN: 4826

European-Finnish (FIN) AF: 0.510 AC: 5401 AN: 10586

Middle Eastern (MID) AF: 0.514 AC: 150 AN: 292

European-Non Finnish (NFE) AF: 0.489 AC: 33216 AN: 67932

Other (OTH) AF: 0.553 AC: 1165 AN: 2108

Alfa AF: 0.445 Hom.: 2878

Bravo AF: 0.584

Asia WGS AF: 0.673 AC: 2343 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	-0.90
CADD	Benign	0.97
DANN	Benign	0.37
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2234161; hg19: chr1-2491205; COSMIC: COSV63185654; COSMIC: COSV63185654;