rs79570196

Variant names:

• chr13-23674374-A-T
• rs79570196
• NM_148957.4:c.*994A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 50 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148957.4. 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
	TNFRSF19	NM_148957.4	MANE Select	c.*994A>T		3_prime_UTR	Exon 10 of 10	NP_683760.1	Q9NS68-2
	TNFRSF19	NM_001204458.3		c.*994A>T		3_prime_UTR	Exon 10 of 10	NP_001191387.1	Q9NS68-2
	TNFRSF19	NM_001354985.2		c.*855A>T		3_prime_UTR	Exon 9 of 9	NP_001341914.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF19	ENST00000248484.9	TSL:1 MANE Select	c.*994A>T		3_prime_UTR	Exon 10 of 10	ENSP00000248484.4	Q9NS68-2
	TNFRSF19	ENST00000382263.3	TSL:1	c.*994A>T		3_prime_UTR	Exon 10 of 10	ENSP00000371698.3	Q9NS68-2
	TNFRSF19	ENST00000862813.1		c.*994A>T		3_prime_UTR	Exon 10 of 10	ENSP00000532872.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.0369 AC: 1536 AN: 41570

American (AMR) AF: 0.0178 AC: 272 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 110 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4832

European-Finnish (FIN) AF: 0.0265 AC: 282 AN: 10622

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0158 AC: 1075 AN: 68030

Other (OTH) AF: 0.0265 AC: 56 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.83
DANN	Benign	0.53
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs79570196; hg19: chr13-24248513;