dbSNP rs141245080: INAVA:p.Arg35Arg (chr1-200891603-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_018265.4(INAVA):c.63G>A(p.Arg21Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,562,954 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R21R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0093 ( 18 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 25 hom. )

Consequence

INAVA
NM_018265.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.588

Publications

2 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: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 1-200891603-G-A is Benign according to our data. Variant chr1-200891603-G-A is described in ClinVar as Benign. ClinVar VariationId is 709585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.588 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00933 (1421/152338) while in subpopulation AFR AF = 0.0318 (1321/41572). AF 95% confidence interval is 0.0304. There are 18 homozygotes in GnomAd4. There are 692 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018265.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INAVA	NM_018265.4		c.63G>A	p.Arg21Arg	synonymous	Exon 1 of 10	NP_060735.4	Q3KP66-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INAVA	ENST00000367342.8	TSL:1	c.105G>A	p.Arg35Arg	synonymous	Exon 1 of 10	ENSP00000356311.5	A0A8V8N8P9
INAVA	ENST00000927411.1		c.-108G>A		5_prime_UTR	Exon 1 of 10	ENSP00000597470.1
INAVA	ENST00000927413.1		c.-193G>A		5_prime_UTR	Exon 1 of 10	ENSP00000597472.1

Frequencies

GnomAD3 genomes

AF:

0.00930

AC:

1415

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0317

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00451

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:

0.000220

Gnomad OTH

AF:

0.00765

GnomAD2 exomes

AF:

0.00270

AC:

510

AN:

189228

AF XY:

0.00206

show subpopulations

Gnomad AFR exome

AF:

0.0361

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000233

Gnomad OTH exome

AF:

0.000237

GnomAD4 exome

AF:

0.00102

AC:

1436

AN:

1410616

Hom.:

Cov.:

AF XY:

0.000888

AC XY:

621

AN XY:

699300

show subpopulations

African (AFR)

AF:

0.0351

AC:

1060

AN:

30166

American (AMR)

AF:

0.00184

AC:

AN:

38630

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22718

East Asian (EAS)

AF:

0.00

AC:

AN:

36116

South Asian (SAS)

AF:

0.000127

AC:

AN:

78938

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51550

Middle Eastern (MID)

AF:

0.00127

AC:

AN:

5500

European-Non Finnish (NFE)

AF:

0.000152

AC:

165

AN:

1088834

Other (OTH)

AF:

0.00211

AC:

123

AN:

58164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

170

254

339

424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.00933

AC:

1421

AN:

152338

Hom.:

Cov.:

AF XY:

0.00929

AC XY:

692

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0318

AC:

1321

AN:

41572

American (AMR)

AF:

0.00451

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000220

AC:

AN:

68032

Other (OTH)

AF:

0.00757

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

137

206

274

343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.000644

Hom.:

Bravo

AF:

0.0108

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

0.59

PromoterAI

-0.22

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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