Variant 1-151158768-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_024575.5(TNFAIP8L2):c.71G>A(p.Arg24His) variant causes a missense change. The variant allele was found at a frequency of 0.00133 in 1,613,898 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00081 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 25 hom. )

Consequence

TNFAIP8L2
NM_024575.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.47

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005941719).

BP6

Variant 1-151158768-G-A is Benign according to our data. Variant chr1-151158768-G-A is described in ClinVar as [Benign]. Clinvar id is 723112.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000808 (123/152156) while in subpopulation SAS AF= 0.0248 (119/4806). AF 95% confidence interval is 0.0211. There are 1 homozygotes in gnomad4. There are 105 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFAIP8L2	NM_024575.5 linkuse as main transcript	c.71G>A	p.Arg24His	missense_variant	2/2	ENST00000368910.4
TNFAIP8L2-SCNM1	NR_144937.2 linkuse as main transcript	n.74+2046G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFAIP8L2	ENST00000368910.4 linkuse as main transcript	c.71G>A	p.Arg24His	missense_variant	2/2	1	NM_024575.5	P1
SCNM1	ENST00000602841.5 linkuse as main transcript	c.-55+2046G>A		intron_variant		3			Q9BWG6-2

Frequencies

GnomAD3 genomes

AF:

0.000809

AC:

123

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0247

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00278

AC:

699

AN:

251228

Hom.:

AF XY:

0.00387

AC XY:

526

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0225

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00139

AC:

2030

AN:

1461742

Hom.:

Cov.:

AF XY:

0.00202

AC XY:

1471

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00169

GnomAD4 genome

AF:

0.000808

AC:

123

AN:

152156

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0248

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000989

Hom.:

Bravo

AF:

0.000159

ExAC

AF:

0.00311

AC:

377

Asia WGS

AF:

0.00953

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.42

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0059

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.34

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

0.99

Vest4

0.17

MVP

0.13

MPC

1.0

ClinPred

0.095

GERP RS

5.7

Varity_R

0.34

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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