Variant 1-200911689-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001142569.3(INAVA):c.1196C>G(p.Ser399Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000592 in 1,614,012 control chromosomes in the GnomAD database, including 9 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 5 hom., cov: 31)

Exomes 𝑓: 0.00033 ( 4 hom. )

Consequence

INAVA
NM_001142569.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.71

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036206841).

BP6

Variant 1-200911689-C-G is Benign according to our data. Variant chr1-200911689-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1690626.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
INAVA	NM_001142569.3 linkuse as main transcript	c.1196C>G	p.Ser399Cys	missense_variant	9/10	ENST00000413687.3	NP_001136041.1
INAVA	NM_018265.4 linkuse as main transcript	c.1451C>G	p.Ser484Cys	missense_variant	9/10		NP_060735.4
INAVA	NM_001367289.1 linkuse as main transcript	c.1196C>G	p.Ser399Cys	missense_variant	9/10		NP_001354218.1
INAVA	NM_001367290.1 linkuse as main transcript	c.659C>G	p.Ser220Cys	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.1196C>G	p.Ser399Cys	missense_variant	9/10	2	NM_001142569.3	ENSP00000392105	P2	Q3KP66-3
INAVA	ENST00000367342.8 linkuse as main transcript	c.1493C>G	p.Ser498Cys	missense_variant	9/10	1		ENSP00000356311	A2

Frequencies

GnomAD3 genomes

AF:

0.00314

AC:

478

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.000869

AC:

218

AN:

250724

Hom.:

AF XY:

0.000634

AC XY:

AN XY:

135584

show subpopulations

Gnomad AFR exome

AF:

0.0127

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000326

AC:

476

AN:

1461696

Hom.:

Cov.:

AF XY:

0.000287

AC XY:

209

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.0124

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.00314

AC:

479

AN:

152316

Hom.:

Cov.:

AF XY:

0.00287

AC XY:

214

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0113

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.00340

ESP6500AA

AF:

0.0107

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00105

AC:

127

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

See cases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

Apr 13, 2021

ACMG classification criteria: BS2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.032

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.46

T;T

MetaRNN

Benign

0.0036

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.017

Sift

Benign

0.29

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.0010

B;.

Vest4

0.17

MVP

0.043

MPC

0.15

ClinPred

0.0021

GERP RS

2.7

Varity_R

0.067

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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