Genetic Variant NM_001142569.3:c.1258G>C (chr1-200911751-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001142569.3(INAVA):c.1258G>C(p.Ala420Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A420T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

INAVA
NM_001142569.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.969

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055241615).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142569.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INAVA	NM_001142569.3	MANE Select	c.1258G>C	p.Ala420Pro	missense	Exon 9 of 10	NP_001136041.1	Q3KP66-3
INAVA	NM_018265.4		c.1513G>C	p.Ala505Pro	missense	Exon 9 of 10	NP_060735.4	Q3KP66-1
INAVA	NM_001367289.1		c.1258G>C	p.Ala420Pro	missense	Exon 9 of 10	NP_001354218.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INAVA	ENST00000413687.3	TSL:2 MANE Select	c.1258G>C	p.Ala420Pro	missense	Exon 9 of 10	ENSP00000392105.2	Q3KP66-3
INAVA	ENST00000367342.8	TSL:1	c.1555G>C	p.Ala519Pro	missense	Exon 9 of 10	ENSP00000356311.5	A0A8V8N8P9
INAVA	ENST00000877560.1		c.1258G>C	p.Ala420Pro	missense	Exon 9 of 10	ENSP00000547619.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000812

AC:

AN:

246274

AF XY:

0.0000150

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459308

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725566

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33428

American (AMR)

AF:

0.00

AC:

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26014

East Asian (EAS)

AF:

0.00

AC:

AN:

39628

South Asian (SAS)

AF:

0.0000349

AC:

AN:

86070

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110476

Other (OTH)

AF:

0.00

AC:

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.2

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0043

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.35

M_CAP

Benign

0.020

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.0

PhyloP100

-0.97

PROVEAN

Benign

-0.91

REVEL

Benign

0.0070

Sift

Benign

0.50

Sift4G

Benign

0.32

Polyphen

0.0020

Vest4

0.13

MutPred

0.45

Loss of helix (P = 0.0093)

MVP

0.043

MPC

0.20

ClinPred

0.018

GERP RS

-1.8

Varity_R

0.092

gMVP

0.36

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over