Genetic Variant INAVA:c.1644+127C>T (chr1-200912264-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001142569.3(INAVA):c.1644+127C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 931,772 control chromosomes in the GnomAD database, including 47,603 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8264 hom., cov: 32)

Exomes 𝑓: 0.31 ( 39339 hom. )

Consequence

INAVA
NM_001142569.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.293

Publications

22 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
INAVA	NM_001142569.3	MANE Select	c.1644+127C>T	intron	N/A	NP_001136041.1	Q3KP66-3
INAVA	NM_018265.4		c.1899+127C>T	intron	N/A	NP_060735.4	Q3KP66-1
INAVA	NM_001367289.1		c.1584+187C>T	intron	N/A	NP_001354218.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
INAVA	ENST00000413687.3	TSL:2 MANE Select	c.1644+127C>T	intron	N/A	ENSP00000392105.2	Q3KP66-3
INAVA	ENST00000367342.8	TSL:1	c.1941+127C>T	intron	N/A	ENSP00000356311.5	A0A8V8N8P9
INAVA	ENST00000877560.1		c.1644+127C>T	intron	N/A	ENSP00000547619.1

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48762

AN:

151882

Hom.:

8258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.409

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.244

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.301

Gnomad OTH

AF:

0.282

GnomAD4 exome

AF:

0.308

AC:

240549

AN:

779772

Hom.:

39339

AF XY:

0.313

AC XY:

122290

AN XY:

390328

show subpopulations

African (AFR)

AF:

0.406

AC:

7360

AN:

18142

American (AMR)

AF:

0.203

AC:

3610

AN:

17796

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

4244

AN:

15398

East Asian (EAS)

AF:

0.231

AC:

7243

AN:

31378

South Asian (SAS)

AF:

0.455

AC:

23565

AN:

51806

European-Finnish (FIN)

AF:

0.235

AC:

6983

AN:

29698

Middle Eastern (MID)

AF:

0.283

AC:

869

AN:

3068

European-Non Finnish (NFE)

AF:

0.305

AC:

175567

AN:

575486

Other (OTH)

AF:

0.300

AC:

11108

AN:

37000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

8359

16719

25078

33438

41797

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4818

9636

14454

19272

24090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.321

AC:

48800

AN:

152000

Hom.:

8264

Cov.:

AF XY:

0.319

AC XY:

23703

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.409

AC:

16944

AN:

41454

American (AMR)

AF:

0.223

AC:

3403

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

955

AN:

3464

East Asian (EAS)

AF:

0.245

AC:

1267

AN:

5180

South Asian (SAS)

AF:

0.471

AC:

2267

AN:

4816

European-Finnish (FIN)

AF:

0.228

AC:

2413

AN:

10580

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.301

AC:

20468

AN:

67920

Other (OTH)

AF:

0.281

AC:

591

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1648

3297

4945

6594

8242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.300

Hom.:

2719

Bravo

AF:

0.320

Asia WGS

AF:

0.347

AC:

1209

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.9

(source)

DANN

Benign

0.79

PhyloP100

-0.29

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over