rs9510787

chr13-23631056-A-Gchr13-23631056-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_148957.4(TNFRSF19):c.445+4264A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,154 control chromosomes in the GnomAD database, including 3,775 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3775 hom., cov: 32)
• Consequence: TNFRSF19 NM_148957.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

Genes affected

TNFRSF19 (HGNC:11915): (TNF receptor superfamily member 19) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is highly expressed during embryonic development. It has been shown to interact with TRAF family members, and to activate JNK signaling pathway when overexpressed in cells. This receptor is capable of inducing apoptosis by a caspase-independent mechanism, and it is thought to play an essential role in embryonic development. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF19	NM_148957.4	c.445+4264A>G		intron_variant		ENST00000248484.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF19	ENST00000248484.9	c.445+4264A>G		intron_variant		1	NM_148957.4	P1
TNFRSF19	ENST00000382258.8	c.445+4264A>G		intron_variant		1
TNFRSF19	ENST00000382263.3	c.445+4264A>G		intron_variant		1		P1
TNFRSF19	ENST00000403372.6	c.49+4264A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30881 AN: 152036 Hom.: 3777 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.216

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.203 AC: 30870 AN: 152154 Hom.: 3775 Cov.: 32 AF XY: 0.199 AC XY: 14802 AN XY: 74386

Gnomad4 AFR AF: 0.0749

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.214

Alfa AF: 0.252 Hom.: 8438

Bravo AF: 0.193

Asia WGS AF: 0.217 AC: 754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.2
Dann	Benign	0.64

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: rs9510787; hg19: chr13-24205195;