Variant 1-200908898-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001142569.3(INAVA):c.743A>T(p.Tyr248Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0112 in 1,613,826 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0077 ( 9 hom., cov: 32)

Exomes 𝑓: 0.012 ( 105 hom. )

Consequence

INAVA
NM_001142569.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 6.87

Variant links:

Genes affected

INAVA (HGNC:25599): (innate immunity activator) Involved in several processes, including nucleotide-binding activity oligomerization domain containing 2 signaling pathway; positive regulation of cytokine production; and positive regulation of intracellular signal transduction. Located in cytoplasm and nucleus. Implicated in inflammatory bowel disease 29. [provided by Alliance of Genome Resources, Apr 2022]

INAVA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008969605).

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
INAVA	NM_001142569.3 linkuse as main transcript	c.743A>T	p.Tyr248Phe	missense_variant	7/10	ENST00000413687.3	NP_001136041.1
INAVA	NM_018265.4 linkuse as main transcript	c.998A>T	p.Tyr333Phe	missense_variant	7/10		NP_060735.4
INAVA	NM_001367289.1 linkuse as main transcript	c.743A>T	p.Tyr248Phe	missense_variant	7/10		NP_001354218.1
INAVA	NM_001367290.1 linkuse as main transcript	c.206A>T	p.Tyr69Phe	missense_variant	7/10		NP_001354219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INAVA	ENST00000413687.3 linkuse as main transcript	c.743A>T	p.Tyr248Phe	missense_variant	7/10	2	NM_001142569.3	ENSP00000392105	P2	Q3KP66-3
INAVA	ENST00000367342.8 linkuse as main transcript	c.1040A>T	p.Tyr347Phe	missense_variant	7/10	1		ENSP00000356311	A2
INAVA	ENST00000526172.1 linkuse as main transcript	n.224A>T		non_coding_transcript_exon_variant	2/4	4

Frequencies

GnomAD3 genomes

AF:

0.00769

AC:

1170

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00884

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0130

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00796

AC:

1967

AN:

247004

Hom.:

AF XY:

0.00762

AC XY:

1022

AN XY:

134048

show subpopulations

Gnomad AFR exome

AF:

0.00305

Gnomad AMR exome

AF:

0.00701

Gnomad ASJ exome

AF:

0.00300

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.00411

Gnomad NFE exome

AF:

0.0134

Gnomad OTH exome

AF:

0.00891

GnomAD4 exome

AF:

0.0116

AC:

16885

AN:

1461610

Hom.:

105

Cov.:

AF XY:

0.0113

AC XY:

8233

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.00194

Gnomad4 AMR exome

AF:

0.00678

Gnomad4 ASJ exome

AF:

0.00287

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00116

Gnomad4 FIN exome

AF:

0.00457

Gnomad4 NFE exome

AF:

0.0140

Gnomad4 OTH exome

AF:

0.00931

GnomAD4 genome

AF:

0.00769

AC:

1170

AN:

152216

Hom.:

Cov.:

AF XY:

0.00719

AC XY:

535

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00212

Gnomad4 AMR

AF:

0.00883

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.0130

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.00968

Hom.:

Bravo

AF:

0.00779

TwinsUK

AF:

0.0170

AC:

ALSPAC

AF:

0.0138

AC:

ESP6500AA

AF:

0.00341

AC:

ESP6500EA

AF:

0.0119

AC:

102

ExAC

AF:

0.00818

AC:

993

Asia WGS

AF:

0.00115

AC:

AN:

3476

EpiCase

AF:

0.0122

EpiControl

AF:

0.0114

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inflammatory bowel disease 29

Pathogenic:1Uncertain:1

Uncertain significance, criteria provided, single submitter	clinical testing	Johns Hopkins Genomics, Johns Hopkins University	Jul 30, 2020	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Oct 09, 2011	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;.

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

D;D

MetaRNN

Benign

0.0090

T;T

MetaSVM

Uncertain

-0.21

MutationTaster

Benign

0.95

D;D

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.28

Sift

Benign

0.068

T;D

Sift4G

Uncertain

0.010

D;D

Polyphen

0.99

D;.

Vest4

0.67

MVP

0.61

MPC

0.64

ClinPred

0.016

GERP RS

5.2

Varity_R

0.33

gMVP

0.11

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