rs77191406

Variant names:

• chr6-137881704-C-T
• rs77191406
• NM_001270508.2:c.*385C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001270508.2(TNFAIP3):​c.*385C>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 0.00211 in 250,212 control chromosomes in the GnomAD database, including 7 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 0.0010 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (6 hom.)
• Consequence: TNFAIP3 NM_001270508.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758
• Publications: 4 publications found

Genes affected

TNFAIP3 (HGNC:11896): (TNF alpha induced protein 3) This gene was identified as a gene whose expression is rapidly induced by the tumor necrosis factor (TNF). The protein encoded by this gene is a zinc finger protein and ubiqitin-editing enzyme, and has been shown to inhibit NF-kappa B activation as well as TNF-mediated apoptosis. The encoded protein, which has both ubiquitin ligase and deubiquitinase activities, is involved in the cytokine-mediated immune and inflammatory responses. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2012]

TNFAIP3 Gene-Disease associations (from GenCC):

• autoinflammatory syndrome, familial, Behcet-like 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hereditary pediatric Behçet-like disease

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287393 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000998 (152/152320) while in subpopulation EAS AF = 0.0266 (138/5188). AF 95% confidence interval is 0.023. There are 1 homozygotes in GnomAd4. There are 80 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 152 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270508.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP3	NM_001270508.2	MANE Select	c.*385C>T		3_prime_UTR	Exon 9 of 9	NP_001257437.1
	TNFAIP3	NM_001270507.2		c.*385C>T		3_prime_UTR	Exon 9 of 9	NP_001257436.1
	TNFAIP3	NM_006290.4		c.*385C>T		3_prime_UTR	Exon 9 of 9	NP_006281.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP3	ENST00000612899.5	TSL:5 MANE Select	c.*385C>T		3_prime_UTR	Exon 9 of 9	ENSP00000481570.1
	TNFAIP3	ENST00000237289.8	TSL:1	c.*385C>T		3_prime_UTR	Exon 9 of 9	ENSP00000237289.4
	TNFAIP3	ENST00000485192.2	TSL:2	n.3379C>T		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes AF: 0.000999 AC: 152 AN: 152202 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0265

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00383 AC: 375 AN: 97892 Hom.: 6 Cov.: 0 AF XY: 0.00329 AC XY: 151 AN XY: 45828

African (AFR) AF: 0.00 AC: 0 AN: 4586

American (AMR) AF: 0.00 AC: 0 AN: 2924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5692

East Asian (EAS) AF: 0.0309 AC: 369 AN: 11960

South Asian (SAS) AF: 0.00 AC: 0 AN: 938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 578

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62128

Other (OTH) AF: 0.000768 AC: 6 AN: 7812

GnomAD4 genome AF: 0.000998 AC: 152 AN: 152320 Hom.: 1 Cov.: 32 AF XY: 0.00107 AC XY: 80 AN XY: 74488

African (AFR) AF: 0.0000241 AC: 1 AN: 41566

American (AMR) AF: 0.000261 AC: 4 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0266 AC: 138 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68018

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.000885 Hom.: 5

Bravo AF: 0.00117

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.64
PhyloP100		-0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs77191406; hg19: chr6-138202841;