rs587777996

Variant names:

• chr1-2559725-G-A
• rs2234160
• NM_003820.4:c.305-98G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-2559725-G-A
• chrNT_187515.1-110915-G-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.305-98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 1,538,132 control chromosomes in the GnomAD database, including 909 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 0.027 (74 hom., cov: 34)
  • Exomes 𝑓: 0.033 (835 hom.)
• Consequence: TNFRSF14 NM_003820.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.66
• Publications: 3 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=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0265 (4042/152294) while in subpopulation NFE AF = 0.0385 (2620/68014). AF 95% confidence interval is 0.0373. There are 74 homozygotes in GnomAd4. There are 1968 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 74 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.305-98G>A		intron	N/A	NP_003811.2
	TNFRSF14	NM_001297605.2		c.305-98G>A		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.305-98G>A		intron	N/A	ENSP00000347948.4
	TNFRSF14	ENST00000475523.5	TSL:1	n.444G>A		non_coding_transcript_exon	Exon 2 of 6
	TNFRSF14	ENST00000860787.1		c.471G>A	p.Ala157Ala	synonymous	Exon 4 of 8	ENSP00000530846.1

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 4043 AN: 152176 Hom.: 74 Cov.: 34

Gnomad AFR AF: 0.00613

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.0375

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0508

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0385

Gnomad OTH AF: 0.0229

GnomAD2 exomes AF: 0.0247 AC: 3493 AN: 141290 AF XY: 0.0247

Gnomad AFR exome AF: 0.00409

Gnomad AMR exome AF: 0.0167

Gnomad ASJ exome AF: 0.0438

Gnomad EAS exome AF: 0.000268

Gnomad FIN exome AF: 0.0563

Gnomad NFE exome AF: 0.0373

Gnomad OTH exome AF: 0.0292

GnomAD4 exome AF: 0.0332 AC: 45964 AN: 1385838 Hom.: 835 Cov.: 99 AF XY: 0.0326 AC XY: 22307 AN XY: 684054

African (AFR) AF: 0.00515 AC: 163 AN: 31680

American (AMR) AF: 0.0169 AC: 605 AN: 35806

Ashkenazi Jewish (ASJ) AF: 0.0414 AC: 1041 AN: 25174

East Asian (EAS) AF: 0.000251 AC: 9 AN: 35886

South Asian (SAS) AF: 0.00457 AC: 362 AN: 79286

European-Finnish (FIN) AF: 0.0577 AC: 2026 AN: 35118

Middle Eastern (MID) AF: 0.0182 AC: 104 AN: 5700

European-Non Finnish (NFE) AF: 0.0370 AC: 39879 AN: 1079242

Other (OTH) AF: 0.0306 AC: 1775 AN: 57946

GnomAD4 genome AF: 0.0265 AC: 4042 AN: 152294 Hom.: 74 Cov.: 34 AF XY: 0.0264 AC XY: 1968 AN XY: 74458

African (AFR) AF: 0.00609 AC: 253 AN: 41568

American (AMR) AF: 0.0271 AC: 414 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0375 AC: 130 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4830

European-Finnish (FIN) AF: 0.0508 AC: 540 AN: 10622

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0385 AC: 2620 AN: 68014

Other (OTH) AF: 0.0227 AC: 48 AN: 2114

Alfa AF: 0.0342 Hom.: 14

Bravo AF: 0.0241

Asia WGS AF: 0.00346 AC: 12 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	-0.89
CADD	Benign	2.4
DANN	Benign	0.43
PhyloP100		-1.7
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)		0.0		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: rs2234160; hg19: chr1-2491164; COSMIC: COSV107449926; COSMIC: COSV107449926;