Variant 1-151159105-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_024575.5(TNFAIP8L2):c.408G>A(p.Thr136Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00516 in 1,614,078 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0053 ( 34 hom. )

Consequence

TNFAIP8L2
NM_024575.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.51

Variant links:

Genes affected

TNFAIP8L2 (HGNC:26277): (TNF alpha induced protein 8 like 2) Predicted to be involved in negative regulation of T cell activation and negative regulation of inflammatory response. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TNFAIP8L2 links:

TNFAIP8L2-SCNM1 (HGNC:):

TNFAIP8L2-SCNM1 links:

SCNM1 (HGNC:23136): (sodium channel modifier 1) SCNM1 is a zinc finger protein and putative splicing factor. In mice, Scnm1 modifies phenotypic expression of Scn8a (MIM 600702) mutations (Buchner et al., 2003 [PubMed 12920299]).[supplied by OMIM, Oct 2009]

SCNM1 links:

LYSMD1 (HGNC:32070): (LysM domain containing 1) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LYSMD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 1-151159105-G-A is Benign according to our data. Variant chr1-151159105-G-A is described in ClinVar as [Benign]. Clinvar id is 708675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.51 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFAIP8L2	NM_024575.5 linkuse as main transcript	c.408G>A	p.Thr136Thr	synonymous_variant	2/2	ENST00000368910.4	NP_078851.2	Q6P589

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP8L2	ENST00000368910.4 linkuse as main transcript	c.408G>A	p.Thr136Thr	synonymous_variant	2/2	1	NM_024575.5	ENSP00000357906.3		Q6P589
SCNM1	ENST00000602841.5 linkuse as main transcript	c.-55+2383G>A		intron_variant		3		ENSP00000473282.1		Q9BWG6-2

Frequencies

GnomAD3 genomes

AF:

0.00353

AC:

538

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00889

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00528

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00427

AC:

1072

AN:

251268

Hom.:

AF XY:

0.00473

AC XY:

643

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.000985

Gnomad AMR exome

AF:

0.00243

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00813

Gnomad FIN exome

AF:

0.000326

Gnomad NFE exome

AF:

0.00579

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00533

AC:

7791

AN:

1461730

Hom.:

Cov.:

AF XY:

0.00542

AC XY:

3938

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.00390

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00758

Gnomad4 FIN exome

AF:

0.000563

Gnomad4 NFE exome

AF:

0.00586

Gnomad4 OTH exome

AF:

0.00482

GnomAD4 genome

AF:

0.00354

AC:

539

AN:

152348

Hom.:

Cov.:

AF XY:

0.00338

AC XY:

252

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00411

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00910

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00528

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00482

Hom.:

Bravo

AF:

0.00362

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00616

EpiControl

AF:

0.00545

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.19

DANN

Benign

0.88

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over