1-200891603-G-T

Variant names:

• chr1-200891603-G-T
• rs141245080
• ENST00000367342.8:c.105G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.588
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -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	c.63G>T	p.Arg21Arg	synonymous_variant	Exon 1 of 10		NP_060735.4

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000317 AC: 6 AN: 189228 AF XY: 0.0000391

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000466

Gnomad OTH exome AF: 0.000237

GnomAD4 exome AF: 0.0000255 AC: 36 AN: 1410622 Hom.: 0 Cov.: 31 AF XY: 0.0000315 AC XY: 22 AN XY: 699304

African (AFR) AF: 0.00 AC: 0 AN: 30172

American (AMR) AF: 0.0000259 AC: 1 AN: 38630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22718

East Asian (EAS) AF: 0.00 AC: 0 AN: 36116

South Asian (SAS) AF: 0.00 AC: 0 AN: 78938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51550

Middle Eastern (MID) AF: 0.000182 AC: 1 AN: 5500

European-Non Finnish (NFE) AF: 0.0000294 AC: 32 AN: 1088834

Other (OTH) AF: 0.0000344 AC: 2 AN: 58164

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	10
DANN	Benign	0.90
PhyloP100		0.59
PromoterAI		-0.21	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs141245080; hg19: chr1-200860731;