chr13-23674374-A-T

Position:

• chr13-23674374-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_148957.4(TNFRSF19):​c.*994A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 152,342 control chromosomes in the GnomAD database, including 50 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 0.022 (50 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNFRSF19 NM_148957.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239

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=-0.86).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0221 (3362/152342) while in subpopulation AFR AF= 0.0369 (1536/41570). AF 95% confidence interval is 0.0354. There are 50 homozygotes in gnomad4. There are 1632 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF19	NM_148957.4	c.*994A>T		3_prime_UTR_variant	10/10	ENST00000248484.9	NP_683760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF19	ENST00000248484.9	c.*994A>T		3_prime_UTR_variant	10/10	1	NM_148957.4	ENSP00000248484.4
TNFRSF19	ENST00000382263.3	c.*994A>T		3_prime_UTR_variant	10/10	1		ENSP00000371698.3
TNFRSF19	ENST00000403372.6	c.*994A>T		3_prime_UTR_variant	8/8	2		ENSP00000385408.2

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3351 AN: 152224 Hom.: 49 Cov.: 33

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0178

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00372

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0158

Gnomad OTH AF: 0.0267

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0221 AC: 3362 AN: 152342 Hom.: 50 Cov.: 33 AF XY: 0.0219 AC XY: 1632 AN XY: 74512

Gnomad4 AFR AF: 0.0369

Gnomad4 AMR AF: 0.0178

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.0265

Gnomad4 NFE AF: 0.0158

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0226 Hom.: 7

Bravo AF: 0.0221

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.83
DANN	Benign	0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs79570196; hg19: chr13-24248513;