rs610604

Variant names:

• chr6-137878280-G-T
• rs610604
• NM_001270508.2:c.987-152G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-137878280-G-T
• chr6-137878280-G-A
• chr6-137878280-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001270508.2(TNFAIP3):​c.987-152G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 658,668 control chromosomes in the GnomAD database, including 146,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (27961 hom., cov: 33)
  • Exomes 𝑓: 0.68 (118448 hom.)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.456
• Publications: 135 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: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• hereditary pediatric Behçet-like disease

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

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287393 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-137878280-G-T is Benign according to our data. Variant chr6-137878280-G-T is described in ClinVar as Benign. ClinVar VariationId is 1275669.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP3	NM_001270508.2	MANE Select	c.987-152G>T		intron	N/A	NP_001257437.1	P21580
	TNFAIP3	NM_001270507.2		c.987-152G>T		intron	N/A	NP_001257436.1	P21580
	TNFAIP3	NM_006290.4		c.987-152G>T		intron	N/A	NP_006281.1	P21580

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP3	ENST00000612899.5	TSL:5 MANE Select	c.987-152G>T		intron	N/A	ENSP00000481570.1	P21580
	TNFAIP3	ENST00000237289.8	TSL:1	c.987-152G>T		intron	N/A	ENSP00000237289.4	P21580
	TNFAIP3	ENST00000420009.6	TSL:3	c.987-152G>T		intron	N/A	ENSP00000401562.2	P21580

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89310 AN: 152008 Hom.: 27957 Cov.: 33

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.610

GnomAD4 exome AF: 0.677 AC: 343131 AN: 506542 Hom.: 118448 AF XY: 0.679 AC XY: 178719 AN XY: 263070

African (AFR) AF: 0.364 AC: 4935 AN: 13542

American (AMR) AF: 0.593 AC: 10694 AN: 18048

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 8732 AN: 14018

East Asian (EAS) AF: 0.921 AC: 28924 AN: 31394

South Asian (SAS) AF: 0.690 AC: 30582 AN: 44330

European-Finnish (FIN) AF: 0.657 AC: 21328 AN: 32460

Middle Eastern (MID) AF: 0.642 AC: 1339 AN: 2086

European-Non Finnish (NFE) AF: 0.676 AC: 218461 AN: 322952

Other (OTH) AF: 0.654 AC: 18136 AN: 27712

GnomAD4 genome AF: 0.587 AC: 89340 AN: 152126 Hom.: 27961 Cov.: 33 AF XY: 0.590 AC XY: 43867 AN XY: 74356

African (AFR) AF: 0.366 AC: 15166 AN: 41490

American (AMR) AF: 0.600 AC: 9177 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2118 AN: 3470

East Asian (EAS) AF: 0.895 AC: 4644 AN: 5186

South Asian (SAS) AF: 0.690 AC: 3330 AN: 4824

European-Finnish (FIN) AF: 0.664 AC: 7015 AN: 10562

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45880 AN: 67974

Other (OTH) AF: 0.608 AC: 1284 AN: 2112

Alfa AF: 0.645 Hom.: 99335

Bravo AF: 0.573

Asia WGS AF: 0.714 AC: 2482 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.44
DANN	Benign	0.59
PhyloP100		-0.46
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

Other links and lift over

dbSNP: rs610604; hg19: chr6-138199417;