1-200891603-G-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_018265.4(INAVA):​c.63G>C​(p.Arg21Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00675 in 1,562,952 control chromosomes in the GnomAD database, including 51 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 0.0043 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0070 (51 hom.)
• Consequence: INAVA NM_018265.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.588

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

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 1-200891603-G-C is Benign according to our data. Variant chr1-200891603-G-C is described in ClinVar as [Benign]. Clinvar id is 779223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.588 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INAVA	NM_018265.4	c.63G>C	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>C	p.Arg35Arg	synonymous_variant	Exon 1 of 10	1		ENSP00000356311.5
INAVA	ENST00000451872.6	c.-10+201G>C		intron_variant	Intron 1 of 4	3		ENSP00000397255.2
INAVA	ENST00000532631.5	c.-95+201G>C		intron_variant	Intron 1 of 2	3		ENSP00000431682.1

Frequencies

GnomAD3 genomes AF: 0.00431 AC: 656 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00801

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00499 AC: 944 AN: 189228 Hom.: 3 AF XY: 0.00483 AC XY: 494 AN XY: 102194

Gnomad AFR exome AF: 0.00114

Gnomad AMR exome AF: 0.000479

Gnomad ASJ exome AF: 0.000176

Gnomad EAS exome AF: 0.0000758

Gnomad SAS exome AF: 0.000550

Gnomad FIN exome AF: 0.00448

Gnomad NFE exome AF: 0.00926

Gnomad OTH exome AF: 0.00522

GnomAD4 exome AF: 0.00702 AC: 9896 AN: 1410608 Hom.: 51 Cov.: 31 AF XY: 0.00671 AC XY: 4693 AN XY: 699296

Gnomad4 AFR exome AF: 0.000862

Gnomad4 AMR exome AF: 0.000544

Gnomad4 ASJ exome AF: 0.000440

Gnomad4 EAS exome AF: 0.0000554

Gnomad4 SAS exome AF: 0.000355

Gnomad4 FIN exome AF: 0.00549

Gnomad4 NFE exome AF: 0.00852

Gnomad4 OTH exome AF: 0.00425

GnomAD4 genome AF: 0.00431 AC: 656 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.00392 AC XY: 292 AN XY: 74500

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00339

Gnomad4 NFE AF: 0.00801

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00162 Hom.: 0

Bravo AF: 0.00402

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	10
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs141245080; hg19: chr1-200860731;