rs710100

Positions:

• chr14-103135941-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371220.1(TNFAIP2):​c.2089A>G​(p.Ile697Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 1,289,572 control chromosomes in the GnomAD database, including 284,839 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (28161 hom., cov: 34)
  • Exomes 𝑓: 0.67 (256678 hom.)
• Consequence: TNFAIP2 NM_001371220.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.880

Genes affected

TNFAIP2 (HGNC:11895): (TNF alpha induced protein 2) This gene was identified as a gene whose expression can be induced by the tumor necrosis factor alpha (TNF) in umbilical vein endothelial cells. The expression of this gene was shown to be induced by retinoic acid in a cell line expressing a oncogenic version of the retinoic acid receptor alpha fusion protein, which suggested that this gene may be a retinoic acid target gene in acute promyelocytic leukemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFAIP2	NM_006291.4	c.*581A>G		3_prime_UTR_variant	12/12	ENST00000560869.6	NP_006282.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP2	ENST00000560869.6	c.*581A>G		3_prime_UTR_variant	12/12	5	NM_006291.4	ENSP00000452634.2
TNFAIP2	ENST00000333007.8	c.*581A>G		3_prime_UTR_variant	13/13	1		ENSP00000332326.1
TNFAIP2	ENST00000559255.1	c.667A>G	p.Ile223Val	missense_variant	5/5	2		ENSP00000452914.2

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90813 AN: 152106 Hom.: 28154 Cov.: 34

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.637

GnomAD3 exomes AF: 0.644 AC: 84255 AN: 130772 Hom.: 27586 AF XY: 0.652 AC XY: 46520 AN XY: 71384

Gnomad AFR exome AF: 0.429

Gnomad AMR exome AF: 0.564

Gnomad ASJ exome AF: 0.723

Gnomad EAS exome AF: 0.633

Gnomad SAS exome AF: 0.688

Gnomad FIN exome AF: 0.603

Gnomad NFE exome AF: 0.681

Gnomad OTH exome AF: 0.679

GnomAD4 exome AF: 0.670 AC: 762063 AN: 1137348 Hom.: 256678 Cov.: 69 AF XY: 0.671 AC XY: 374394 AN XY: 557938

Gnomad4 AFR exome AF: 0.426

Gnomad4 AMR exome AF: 0.569

Gnomad4 ASJ exome AF: 0.717

Gnomad4 EAS exome AF: 0.627

Gnomad4 SAS exome AF: 0.682

Gnomad4 FIN exome AF: 0.611

Gnomad4 NFE exome AF: 0.679

Gnomad4 OTH exome AF: 0.673

GnomAD4 genome AF: 0.597 AC: 90846 AN: 152224 Hom.: 28161 Cov.: 34 AF XY: 0.593 AC XY: 44159 AN XY: 74434

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.640

Alfa AF: 0.671 Hom.: 48440

Bravo AF: 0.591

Asia WGS AF: 0.708 AC: 2460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs710100; hg19: chr14-103602278; COSMIC: COSV60693820; COSMIC: COSV60693820;