Variant 1-200911751-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001142569.3(INAVA):c.1258G>A(p.Ala420Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,459,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

INAVA
NM_001142569.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.969

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039504796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
INAVA	NM_001142569.3 linkuse as main transcript	c.1258G>A	p.Ala420Thr	missense_variant	9/10	ENST00000413687.3	NP_001136041.1
INAVA	NM_018265.4 linkuse as main transcript	c.1513G>A	p.Ala505Thr	missense_variant	9/10		NP_060735.4
INAVA	NM_001367289.1 linkuse as main transcript	c.1258G>A	p.Ala420Thr	missense_variant	9/10		NP_001354218.1
INAVA	NM_001367290.1 linkuse as main transcript	c.721G>A	p.Ala241Thr	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.1258G>A	p.Ala420Thr	missense_variant	9/10	2	NM_001142569.3	ENSP00000392105	P2	Q3KP66-3
INAVA	ENST00000367342.8 linkuse as main transcript	c.1555G>A	p.Ala519Thr	missense_variant	9/10	1		ENSP00000356311	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000203

AC:

AN:

246274

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133712

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000453

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000822

AC:

AN:

1459306

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725564

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000566

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 2021

The c.1555G>A (p.A519T) alteration is located in exon 9 (coding exon 9) of the C1orf106 gene. This alteration results from a G to A substitution at nucleotide position 1555, causing the alanine (A) at amino acid position 519 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.7

DANN

Benign

0.85

DEOGEN2

Benign

0.00078

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.39

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.040

T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

0.0

N;N

REVEL

Benign

0.0020

Sift

Benign

0.92

T;T

Sift4G

Benign

0.54

T;T

Polyphen

0.0020

B;.

Vest4

0.062

MVP

0.043

MPC

0.15

ClinPred

0.018

GERP RS

-1.8

Varity_R

0.030

gMVP

0.27

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