ENST00000274456.6:c.2-51982T>C

Variant names:

• chr5-119340834-T-C
• rs10519585
• ENST00000274456.6:c.2-51982T>C

Variant summary

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

The ENST00000274456.6(TNFAIP8):​c.2-51982T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,992 control chromosomes in the GnomAD database, including 10,494 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 0.36 (10494 hom., cov: 31)
• Consequence: TNFAIP8 ENST00000274456.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• Publications: 5 publications found

Genes affected

TNFAIP8 (HGNC:17260): (TNF alpha induced protein 8) Enables cysteine-type endopeptidase inhibitor activity involved in apoptotic process. Involved in positive regulation of apoptotic process. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LOC102723444 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000274456.6. 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
	TNFAIP8	NM_001286814.1		c.67+7203T>C		intron	N/A	NP_001273743.1	O95379-4
	TNFAIP8	NM_001077654.3		c.2-51982T>C		intron	N/A	NP_001071122.1	O95379-3
	TNFAIP8	NM_001286815.2		c.-66+24532T>C		intron	N/A	NP_001273744.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP8	ENST00000274456.6	TSL:1	c.2-51982T>C		intron	N/A	ENSP00000274456.6	O95379-3
	TNFAIP8	ENST00000513374.1	TSL:2	c.67+7203T>C		intron	N/A	ENSP00000427424.1	O95379-4
	TNFAIP8	ENST00000388882.5	TSL:4	c.-66+24532T>C		intron	N/A	ENSP00000429432.1	E5RIJ3

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54103 AN: 151874 Hom.: 10479 Cov.: 31

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.0611

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.356 AC: 54174 AN: 151992 Hom.: 10494 Cov.: 31 AF XY: 0.356 AC XY: 26424 AN XY: 74286

African (AFR) AF: 0.511 AC: 21175 AN: 41414

American (AMR) AF: 0.299 AC: 4575 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1056 AN: 3468

East Asian (EAS) AF: 0.0611 AC: 316 AN: 5174

South Asian (SAS) AF: 0.222 AC: 1069 AN: 4818

European-Finnish (FIN) AF: 0.354 AC: 3739 AN: 10554

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21046 AN: 67976

Other (OTH) AF: 0.321 AC: 677 AN: 2106

Alfa AF: 0.319 Hom.: 14016

Bravo AF: 0.358

Asia WGS AF: 0.169 AC: 587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.47
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10519585;

hg19: chr5-118676529;

COSMIC: COSV57226161;