chr14-103135941-A-G

Variant names:

• chr14-103135941-A-G
• rs710100
• NM_006291.4:c.*581A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006291.4(TNFAIP2):​c.*581A>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 0.661 in 1,289,572 control chromosomes in the GnomAD database, including 284,839 homozygotes. In-silico tool predicts a benign outcome for this variant. 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_006291.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.880
• Publications: 28 publications found

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

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

• BP4: Computational evidence support a benign effect (REVEL=0.011).
• 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 rank	MANE	Protein	UniProt
TNFAIP2	NM_006291.4	c.*581A>G		3_prime_UTR_variant	Exon 12 of 12	ENST00000560869.6	NP_006282.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFAIP2	ENST00000560869.6	c.*581A>G		3_prime_UTR_variant	Exon 12 of 12	5	NM_006291.4	ENSP00000452634.2
TNFAIP2	ENST00000333007.8	c.*581A>G		3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000332326.1
TNFAIP2	ENST00000559255.2	c.2089A>G	p.Ile697Val	missense_variant	Exon 13 of 13	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

GnomAD2 exomes AF: 0.644 AC: 84255 AN: 130772 AF XY: 0.652

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 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

African (AFR) AF: 0.426 AC: 10403 AN: 24432

American (AMR) AF: 0.569 AC: 16085 AN: 28272

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 11434 AN: 15944

East Asian (EAS) AF: 0.627 AC: 8075 AN: 12876

South Asian (SAS) AF: 0.682 AC: 51947 AN: 76204

European-Finnish (FIN) AF: 0.611 AC: 7746 AN: 12668

Middle Eastern (MID) AF: 0.686 AC: 3015 AN: 4398

European-Non Finnish (NFE) AF: 0.679 AC: 625402 AN: 921012

Other (OTH) AF: 0.673 AC: 27956 AN: 41542

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

African (AFR) AF: 0.430 AC: 17869 AN: 41540

American (AMR) AF: 0.590 AC: 9033 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2505 AN: 3468

East Asian (EAS) AF: 0.644 AC: 3337 AN: 5178

South Asian (SAS) AF: 0.676 AC: 3266 AN: 4828

European-Finnish (FIN) AF: 0.596 AC: 6322 AN: 10612

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.680 AC: 46240 AN: 67980

Other (OTH) AF: 0.640 AC: 1352 AN: 2114

Alfa AF: 0.664 Hom.: 59615

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
PhyloP100		-0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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