Variant 1-200911850-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001142569.3(INAVA):c.1357C>T(p.Arg453Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 1,564,990 control chromosomes in the GnomAD database, including 433,656 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 40624 hom., cov: 31)

Exomes 𝑓: 0.74 ( 393032 hom. )

Consequence

INAVA
NM_001142569.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.650

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.791483E-7).

BP6

Variant 1-200911850-C-T is Benign according to our data. Variant chr1-200911850-C-T is described in ClinVar as [Benign]. Clinvar id is 767740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
INAVA	NM_001142569.3 linkuse as main transcript	c.1357C>T	p.Arg453Cys	missense_variant	9/10	ENST00000413687.3	NP_001136041.1
INAVA	NM_018265.4 linkuse as main transcript	c.1612C>T	p.Arg538Cys	missense_variant	9/10		NP_060735.4
INAVA	NM_001367289.1 linkuse as main transcript	c.1357C>T	p.Arg453Cys	missense_variant	9/10		NP_001354218.1
INAVA	NM_001367290.1 linkuse as main transcript	c.820C>T	p.Arg274Cys	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.1357C>T	p.Arg453Cys	missense_variant	9/10	2	NM_001142569.3	ENSP00000392105	P2	Q3KP66-3
INAVA	ENST00000367342.8 linkuse as main transcript	c.1654C>T	p.Arg552Cys	missense_variant	9/10	1		ENSP00000356311	A2

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110159

AN:

151864

Hom.:

40592

Cov.:

show subpopulations

Gnomad AFR

AF:

0.629

Gnomad AMI

AF:

0.546

Gnomad AMR

AF:

0.814

Gnomad ASJ

AF:

0.761

Gnomad EAS

AF:

0.995

Gnomad SAS

AF:

0.856

Gnomad FIN

AF:

0.805

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.721

Gnomad OTH

AF:

0.756

GnomAD3 exomes

AF:

0.788

AC:

161920

AN:

205608

Hom.:

65262

AF XY:

0.788

AC XY:

89575

AN XY:

113656

show subpopulations

Gnomad AFR exome

AF:

0.619

Gnomad AMR exome

AF:

0.878

Gnomad ASJ exome

AF:

0.782

Gnomad EAS exome

AF:

0.997

Gnomad SAS exome

AF:

0.859

Gnomad FIN exome

AF:

0.796

Gnomad NFE exome

AF:

0.719

Gnomad OTH exome

AF:

0.786

GnomAD4 exome

AF:

0.740

AC:

1045789

AN:

1413008

Hom.:

393032

Cov.:

AF XY:

0.744

AC XY:

522464

AN XY:

702434

show subpopulations

Gnomad4 AFR exome

AF:

0.627

Gnomad4 AMR exome

AF:

0.872

Gnomad4 ASJ exome

AF:

0.763

Gnomad4 EAS exome

AF:

0.986

Gnomad4 SAS exome

AF:

0.854

Gnomad4 FIN exome

AF:

0.792

Gnomad4 NFE exome

AF:

0.717

Gnomad4 OTH exome

AF:

0.753

GnomAD4 genome

AF:

0.725

AC:

110239

AN:

151982

Hom.:

40624

Cov.:

AF XY:

0.735

AC XY:

54603

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.629

Gnomad4 AMR

AF:

0.814

Gnomad4 ASJ

AF:

0.761

Gnomad4 EAS

AF:

0.995

Gnomad4 SAS

AF:

0.856

Gnomad4 FIN

AF:

0.805

Gnomad4 NFE

AF:

0.721

Gnomad4 OTH

AF:

0.759

Alfa

AF:

0.710

Hom.:

4893

Bravo

AF:

0.721

ESP6500AA

AF:

0.629

AC:

2547

ESP6500EA

AF:

0.703

AC:

5587

ExAC

AF:

0.751

AC:

86818

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	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.9

DANN

Benign

0.32

DEOGEN2

Benign

0.0016

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.30

T;T

MetaRNN

Benign

7.8e-7

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.016

Sift

Benign

0.28

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.0

B;.

Vest4

0.041

MPC

2.2

ClinPred

0.0080

GERP RS

0.76

Varity_R

0.056

gMVP

0.53

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