rs587777979

chr1-2559074-C-GchrNT_187515.1-110263-C-Gchr1-2559074-C-TchrNT_187515.1-110263-C-Tchr1-2559074-C-AchrNT_187515.1-110263-C-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_003820.4(TNFRSF14):c.304+606C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,368,990 control chromosomes in the GnomAD database, including 42 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 0.010 (18 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (24 hom.)
• Consequence: TNFRSF14 NM_003820.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -2.00

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

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0104 (1586/152334) while in subpopulation AFR AF= 0.0356 (1480/41570). AF 95% confidence interval is 0.0341. There are 18 homozygotes in gnomad4. There are 734 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF14	NM_003820.4	c.304+606C>G		intron_variant		ENST00000355716.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF14	ENST00000355716.5	c.304+606C>G		intron_variant		1	NM_003820.4	P1

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1580 AN: 152216 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0355

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00765

GnomAD3 exomes AF: 0.00232 AC: 303 AN: 130366 Hom.: 5 AF XY: 0.00200 AC XY: 142 AN XY: 71094

Gnomad AFR exome AF: 0.0371

Gnomad AMR exome AF: 0.00259

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000894

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000607

Gnomad OTH exome AF: 0.000494

GnomAD4 exome AF: 0.00110 AC: 1343 AN: 1216656 Hom.: 24 Cov.: 30 AF XY: 0.000981 AC XY: 583 AN XY: 594314

Gnomad4 AFR exome AF: 0.0383

Gnomad4 AMR exome AF: 0.00248

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000911

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000340

Gnomad4 OTH exome AF: 0.00295

GnomAD4 genome AF: 0.0104 AC: 1586 AN: 152334 Hom.: 18 Cov.: 33 AF XY: 0.00985 AC XY: 734 AN XY: 74494

Gnomad4 AFR AF: 0.0356

Gnomad4 AMR AF: 0.00503

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.000560 Hom.: 2

Bravo AF: 0.0116

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.36
Dann	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs11573976; hg19: chr1-2490513; COSMIC: COSV63187909; COSMIC: COSV63187909;