Genetic Variant TNFAIP8:c.*312A>G (chr5-119393693-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014350.4(TNFAIP8):c.*312A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 271,980 control chromosomes in the GnomAD database, including 8,658 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 0.27 ( 5460 hom., cov: 32)

Exomes 𝑓: 0.22 ( 3198 hom. )

Consequence

TNFAIP8
NM_014350.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.634

Publications

27 publications found

Variant links:

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]

TNFAIP8 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014350.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TNFAIP8	NM_014350.4	MANE Select	c.*312A>G	3_prime_UTR	Exon 2 of 2	NP_055165.2
TNFAIP8	NM_001286814.1		c.*312A>G	3_prime_UTR	Exon 2 of 2	NP_001273743.1
TNFAIP8	NM_001286813.2		c.*312A>G	3_prime_UTR	Exon 3 of 3	NP_001273742.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TNFAIP8	ENST00000504771.3	TSL:1 MANE Select	c.*312A>G	3_prime_UTR	Exon 2 of 2	ENSP00000422245.1
TNFAIP8	ENST00000415806.2	TSL:1	c.*908A>G	3_prime_UTR	Exon 3 of 3	ENSP00000408534.2
TNFAIP8	ENST00000513374.1	TSL:2	c.*312A>G	3_prime_UTR	Exon 2 of 2	ENSP00000427424.1

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40493

AN:

152060

Hom.:

5457

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.427

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.0992

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.271

GnomAD4 exome

AF:

0.222

AC:

26549

AN:

119802

Hom.:

3198

Cov.:

AF XY:

0.219

AC XY:

13650

AN XY:

62380

show subpopulations

African (AFR)

AF:

0.230

AC:

981

AN:

4262

American (AMR)

AF:

0.243

AC:

1341

AN:

5508

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

806

AN:

3754

East Asian (EAS)

AF:

0.0945

AC:

792

AN:

8384

South Asian (SAS)

AF:

0.152

AC:

1736

AN:

11390

European-Finnish (FIN)

AF:

0.253

AC:

1185

AN:

4678

Middle Eastern (MID)

AF:

0.229

AC:

119

AN:

520

European-Non Finnish (NFE)

AF:

0.243

AC:

18104

AN:

74472

Other (OTH)

AF:

0.217

AC:

1485

AN:

6834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

920

1841

2761

3682

4602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

158

316

474

632

790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.266

AC:

40504

AN:

152178

Hom.:

5460

Cov.:

AF XY:

0.266

AC XY:

19760

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.266

AC:

11043

AN:

41532

American (AMR)

AF:

0.243

AC:

3724

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

870

AN:

3472

East Asian (EAS)

AF:

0.0991

AC:

514

AN:

5188

South Asian (SAS)

AF:

0.194

AC:

934

AN:

4826

European-Finnish (FIN)

AF:

0.310

AC:

3271

AN:

10552

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.281

AC:

19122

AN:

67998

Other (OTH)

AF:

0.267

AC:

564

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1528

3055

4583

6110

7638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.273

Hom.:

8928

Bravo

AF:

0.262

Asia WGS

AF:

0.149

AC:

515

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

4.5

(source)

DANN

Benign

0.72

PhyloP100

0.63

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over