Variant 1-200911898-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001142569.3(INAVA):c.1405C>T(p.Arg469Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,581,504 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 4 hom. )

Consequence

INAVA
NM_001142569.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.982

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=0.0074567795).

BP6

Variant 1-200911898-C-T is Benign according to our data. Variant chr1-200911898-C-T is described in ClinVar as [Benign]. Clinvar id is 781799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
INAVA	NM_001142569.3 linkuse as main transcript	c.1405C>T	p.Arg469Cys	missense_variant	9/10	ENST00000413687.3	NP_001136041.1
INAVA	NM_018265.4 linkuse as main transcript	c.1660C>T	p.Arg554Cys	missense_variant	9/10		NP_060735.4
INAVA	NM_001367289.1 linkuse as main transcript	c.1405C>T	p.Arg469Cys	missense_variant	9/10		NP_001354218.1
INAVA	NM_001367290.1 linkuse as main transcript	c.868C>T	p.Arg290Cys	missense_variant	9/10		NP_001354219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INAVA	ENST00000413687.3 linkuse as main transcript	c.1405C>T	p.Arg469Cys	missense_variant	9/10	2	NM_001142569.3	ENSP00000392105	P2	Q3KP66-3
INAVA	ENST00000367342.8 linkuse as main transcript	c.1702C>T	p.Arg568Cys	missense_variant	9/10	1		ENSP00000356311	A2

Frequencies

GnomAD3 genomes

AF:

0.00102

AC:

155

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00135

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00111

AC:

217

AN:

195798

Hom.:

AF XY:

0.00108

AC XY:

118

AN XY:

108938

show subpopulations

Gnomad AFR exome

AF:

0.000268

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00721

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00101

Gnomad OTH exome

AF:

0.00316

GnomAD4 exome

AF:

0.00110

AC:

1571

AN:

1429148

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

810

AN XY:

709930

show subpopulations

Gnomad4 AFR exome

AF:

0.000850

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.00849

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000179

Gnomad4 FIN exome

AF:

0.0000502

Gnomad4 NFE exome

AF:

0.000995

Gnomad4 OTH exome

AF:

0.00197

GnomAD4 genome

AF:

0.00102

AC:

155

AN:

152356

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00135

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00170

Hom.:

Bravo

AF:

0.000979

ExAC

AF:

0.000912

AC:

106

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 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.79

T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.0075

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PROVEAN

Uncertain

-3.6

D;D

REVEL

Benign

0.15

Sift

Benign

0.041

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.047

B;.

Vest4

0.39

MVP

0.12

MPC

2.3

ClinPred

0.025

GERP RS

4.4

Varity_R

0.14

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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