Genetic Variant ENST00000367342.8:c.105G>T (chr1-200891603-G-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The ENST00000367342.8(INAVA):c.105G>T(p.Arg35Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,410,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R35R) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

INAVA
ENST00000367342.8 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.588

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 -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP7

Synonymous conserved (PhyloP=0.588 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INAVA	NM_018265.4 link	c.63G>T	p.Arg21Arg	synonymous_variant	Exon 1 of 10		NP_060735.4	Q3KP66-1A0A8V8N8P9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
INAVA	ENST00000367342.8 link	c.105G>T	p.Arg35Arg	synonymous_variant	Exon 1 of 10	1	ENSP00000356311.5	A0A8V8N8P9
INAVA	ENST00000451872.6 link	c.-10+201G>T		intron_variant	Intron 1 of 4	3	ENSP00000397255.2	C9JAT8
INAVA	ENST00000532631.5 link	c.-95+201G>T		intron_variant	Intron 1 of 2	3	ENSP00000431682.1	E9PK29

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000317

AC:

AN:

189228

Hom.:

AF XY:

0.0000391

AC XY:

AN XY:

102194

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000368

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:

0.0000466

Gnomad OTH exome

AF:

0.000237

GnomAD4 exome

AF:

0.0000255

AC:

AN:

1410622

Hom.:

Cov.:

AF XY:

0.0000315

AC XY:

AN XY:

699304

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000259

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:

0.0000294

Gnomad4 OTH exome

AF:

0.0000344

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.90

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over