1-200898444-T-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001142569.3(INAVA):c.44T>A(p.Ile15Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0094 in 1,613,962 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0097 ( 95 hom. )

Consequence

INAVA
NM_001142569.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.69

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070993304).

BP6

Variant 1-200898444-T-A is Benign according to our data. Variant chr1-200898444-T-A is described in ClinVar as [Benign]. Clinvar id is 786759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
INAVA	NM_001142569.3 linkuse as main transcript	c.44T>A	p.Ile15Asn	missense_variant	2/10	ENST00000413687.3
INAVA	NM_018265.4 linkuse as main transcript	c.299T>A	p.Ile100Asn	missense_variant	2/10
INAVA	NM_001367289.1 linkuse as main transcript	c.44T>A	p.Ile15Asn	missense_variant	2/10
INAVA	NM_001367290.1 linkuse as main transcript	c.-492T>A		5_prime_UTR_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INAVA	ENST00000413687.3 linkuse as main transcript	c.44T>A	p.Ile15Asn	missense_variant	2/10	2	NM_001142569.3	P2	Q3KP66-3
INAVA	ENST00000367342.8 linkuse as main transcript	c.341T>A	p.Ile114Asn	missense_variant	2/10	1		A2
INAVA	ENST00000451872.6 linkuse as main transcript	c.44T>A	p.Ile15Asn	missense_variant	2/5	3
INAVA	ENST00000532631.5 linkuse as main transcript	c.44T>A	p.Ile15Asn	missense_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.00687

AC:

1045

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00751

AC:

1888

AN:

251340

Hom.:

AF XY:

0.00747

AC XY:

1014

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00923

Gnomad ASJ exome

AF:

0.00894

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00301

Gnomad FIN exome

AF:

0.00208

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.00966

AC:

14122

AN:

1461750

Hom.:

Cov.:

AF XY:

0.00941

AC XY:

6845

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.0102

Gnomad4 ASJ exome

AF:

0.00834

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00368

Gnomad4 FIN exome

AF:

0.00264

Gnomad4 NFE exome

AF:

0.0111

Gnomad4 OTH exome

AF:

0.00894

GnomAD4 genome

AF:

0.00686

AC:

1044

AN:

152212

Hom.:

Cov.:

AF XY:

0.00654

AC XY:

487

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00927

Hom.:

Bravo

AF:

0.00782

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0115

AC:

ExAC

AF:

0.00742

AC:

901

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0129

EpiControl

AF:

0.0129

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	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	INAVA: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jun 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Benign

0.17

T;T;T;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.93

D;D;D;D

MetaRNN

Benign

0.0071

T;T;T;T

MetaSVM

Benign

-0.57

MutationTaster

Benign

1.0

D;D

PROVEAN

Pathogenic

-6.5

D;D;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

.;.;D;.

Vest4

0.89, 0.80

MVP

0.33

MPC

0.90

ClinPred

0.028

GERP RS

5.0

Varity_R

0.91

gMVP

0.89

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