rs73222601

Variant names:

• chr8-23222536-A-G
• rs73222601
• NM_003844.4:c.306+2220T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003844.4(TNFRSF10A):​c.306+2220T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,190 control chromosomes in the GnomAD database, including 4,056 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 0.21 (4056 hom., cov: 32)
• Consequence: TNFRSF10A NM_003844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 4 publications found

Genes affected

TNFRSF10A (HGNC:11904): (TNF receptor superfamily member 10a) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL), and thus transduces cell death signal and induces cell apoptosis. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein. [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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10A	NM_003844.4	c.306+2220T>C		intron_variant	Intron 1 of 9	ENST00000221132.8	NP_003835.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10A	ENST00000221132.8	c.306+2220T>C		intron_variant	Intron 1 of 9	1	NM_003844.4	ENSP00000221132.3
TNFRSF10A	ENST00000613472.1	c.31+2495T>C		intron_variant	Intron 1 of 8	1		ENSP00000480778.1
TNFRSF10A	ENST00000524158.5	c.-301+1897T>C		intron_variant	Intron 1 of 6	5		ENSP00000428884.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31834 AN: 152072 Hom.: 4051 Cov.: 32

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.209 AC: 31852 AN: 152190 Hom.: 4056 Cov.: 32 AF XY: 0.214 AC XY: 15891 AN XY: 74398

African (AFR) AF: 0.0623 AC: 2590 AN: 41556

American (AMR) AF: 0.322 AC: 4916 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3472

East Asian (EAS) AF: 0.288 AC: 1489 AN: 5178

South Asian (SAS) AF: 0.395 AC: 1903 AN: 4822

European-Finnish (FIN) AF: 0.223 AC: 2357 AN: 10588

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16735 AN: 67984

Other (OTH) AF: 0.243 AC: 513 AN: 2110

Alfa AF: 0.228 Hom.: 1864

Bravo AF: 0.208

Asia WGS AF: 0.329 AC: 1145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.69
DANN	Benign	0.33
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73222601; hg19: chr8-23080049;