rs661561

Variant names:

• chr6-137876194-A-C
• rs661561
• NM_001270508.2:c.805+28A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-137876194-A-C
• chr6-137876194-A-G
• chr6-137876194-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006290.4(TNFAIP3):​c.805+28A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 1,583,506 control chromosomes in the GnomAD database, including 319,081 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (23620 hom., cov: 32)
  • Exomes 𝑓: 0.64 (295461 hom.)
• Consequence: TNFAIP3 NM_006290.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.50
• Publications: 30 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-137876194-A-C is Benign according to our data. Variant chr6-137876194-A-C is described in ClinVar as Benign. ClinVar VariationId is 1281403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006290.4. 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.805+28A>C		intron	N/A	NP_001257437.1
	TNFAIP3	NM_001270507.2		c.805+28A>C		intron	N/A	NP_001257436.1
	TNFAIP3	NM_006290.4		c.805+28A>C		intron	N/A	NP_006281.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP3	ENST00000612899.5	TSL:5 MANE Select	c.805+28A>C		intron	N/A	ENSP00000481570.1
	TNFAIP3	ENST00000237289.8	TSL:1	c.805+28A>C		intron	N/A	ENSP00000237289.4
	TNFAIP3	ENST00000420009.6	TSL:3	c.805+28A>C		intron	N/A	ENSP00000401562.2

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78072 AN: 152004 Hom.: 23623 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.550

GnomAD2 exomes AF: 0.620 AC: 148964 AN: 240196 AF XY: 0.631

Gnomad AFR exome AF: 0.171

Gnomad AMR exome AF: 0.577

Gnomad ASJ exome AF: 0.592

Gnomad EAS exome AF: 0.856

Gnomad FIN exome AF: 0.640

Gnomad NFE exome AF: 0.647

Gnomad OTH exome AF: 0.631

GnomAD4 exome AF: 0.637 AC: 911558 AN: 1431386 Hom.: 295461 Cov.: 25 AF XY: 0.639 AC XY: 455444 AN XY: 712590

African (AFR) AF: 0.164 AC: 5259 AN: 32110

American (AMR) AF: 0.574 AC: 23781 AN: 41464

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 14780 AN: 25322

East Asian (EAS) AF: 0.859 AC: 33881 AN: 39450

South Asian (SAS) AF: 0.661 AC: 54737 AN: 82786

European-Finnish (FIN) AF: 0.640 AC: 34050 AN: 53182

Middle Eastern (MID) AF: 0.600 AC: 3412 AN: 5688

European-Non Finnish (NFE) AF: 0.646 AC: 705231 AN: 1092142

Other (OTH) AF: 0.615 AC: 36427 AN: 59242

GnomAD4 genome AF: 0.513 AC: 78071 AN: 152120 Hom.: 23620 Cov.: 32 AF XY: 0.518 AC XY: 38547 AN XY: 74360

African (AFR) AF: 0.175 AC: 7245 AN: 41502

American (AMR) AF: 0.561 AC: 8577 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1982 AN: 3472

East Asian (EAS) AF: 0.852 AC: 4423 AN: 5190

South Asian (SAS) AF: 0.664 AC: 3201 AN: 4822

European-Finnish (FIN) AF: 0.647 AC: 6828 AN: 10558

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 43950 AN: 67968

Other (OTH) AF: 0.547 AC: 1156 AN: 2112

Alfa AF: 0.610 Hom.: 37801

Bravo AF: 0.494

Asia WGS AF: 0.673 AC: 2339 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autoinflammatory syndrome, familial, Behcet-like (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.42
PhyloP100		-2.5
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: rs661561; hg19: chr6-138197331; COSMIC: COSV52801907; COSMIC: COSV52801907;