NM_021137.5:c.618C>T

Variant names:

• chr17-28342346-C-T
• rs3093722
• NM_021137.5:c.618C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_021137.5(TNFAIP1):​c.618C>T​(p.Asp206Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00562 in 1,607,540 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (71 hom.)
• Consequence: TNFAIP1 NM_021137.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.83
• Publications: 2 publications found

Genes affected

TNFAIP1 (HGNC:11894): (TNF alpha induced protein 1) This gene was identified as a gene whose expression can be induced by the tumor necrosis factor alpha (TNF) in umbilical vein endothelial cells. Studies of a similar gene in mouse suggest that the expression of this gene is developmentally regulated in a tissue-specific manner. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 17-28342346-C-T is Benign according to our data. Variant chr17-28342346-C-T is described in ClinVar as Benign. ClinVar VariationId is 3024741.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.84 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021137.5. 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
	TNFAIP1	NM_021137.5	MANE Select	c.618C>T	p.Asp206Asp	synonymous	Exon 6 of 7	NP_066960.1	Q13829-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP1	ENST00000226225.7	TSL:1 MANE Select	c.618C>T	p.Asp206Asp	synonymous	Exon 6 of 7	ENSP00000226225.2	Q13829-1
	TNFAIP1	ENST00000902207.1		c.618C>T	p.Asp206Asp	synonymous	Exon 7 of 8	ENSP00000572266.1
	TNFAIP1	ENST00000902210.1		c.618C>T	p.Asp206Asp	synonymous	Exon 7 of 8	ENSP00000572269.1

Frequencies

GnomAD3 genomes AF: 0.00592 AC: 901 AN: 152224 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00829

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00592 AC: 1489 AN: 251318 AF XY: 0.00571

Gnomad AFR exome AF: 0.000739

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00338

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00828

Gnomad NFE exome AF: 0.0104

Gnomad OTH exome AF: 0.00603

GnomAD4 exome AF: 0.00559 AC: 8138 AN: 1455198 Hom.: 71 Cov.: 33 AF XY: 0.00571 AC XY: 4129 AN XY: 722650

African (AFR) AF: 0.000659 AC: 22 AN: 33392

American (AMR) AF: 0.00114 AC: 51 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00434 AC: 113 AN: 26060

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39464

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86068

European-Finnish (FIN) AF: 0.00858 AC: 458 AN: 53352

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5750

European-Non Finnish (NFE) AF: 0.00650 AC: 7193 AN: 1106394

Other (OTH) AF: 0.00496 AC: 298 AN: 60066

GnomAD4 genome AF: 0.00591 AC: 901 AN: 152342 Hom.: 5 Cov.: 32 AF XY: 0.00549 AC XY: 409 AN XY: 74504

African (AFR) AF: 0.000794 AC: 33 AN: 41572

American (AMR) AF: 0.00163 AC: 25 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00829 AC: 88 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0106 AC: 721 AN: 68038

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00859 Hom.: 11

Bravo AF: 0.00445

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00809

EpiControl AF: 0.00546

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	-0.61
CADD	Benign	5.8
DANN	Benign	0.90
PhyloP100		-1.8
Mutation Taster		=98/2	polymorphism

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: rs3093722; hg19: chr17-26669372;