NM_001142569.3:c.255C>T

Variant names:

• chr1-200900178-C-T
• rs34596202
• NM_001142569.3:c.255C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001142569.3(INAVA):​c.255C>T​(p.Ile85Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,614,140 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (4 hom.)
• Consequence: INAVA NM_001142569.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.68
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 1-200900178-C-T is Benign according to our data. Variant chr1-200900178-C-T is described in ClinVar as Benign. ClinVar VariationId is 781798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.68 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INAVA	NM_001142569.3	MANE Select	c.255C>T	p.Ile85Ile	synonymous	Exon 4 of 10	NP_001136041.1	Q3KP66-3
	INAVA	NM_001367290.1		c.-281C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 10	NP_001354219.1
	INAVA	NM_018265.4		c.510C>T	p.Ile170Ile	synonymous	Exon 4 of 10	NP_060735.4	Q3KP66-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INAVA	ENST00000413687.3	TSL:2 MANE Select	c.255C>T	p.Ile85Ile	synonymous	Exon 4 of 10	ENSP00000392105.2	Q3KP66-3
	INAVA	ENST00000367342.8	TSL:1	c.552C>T	p.Ile184Ile	synonymous	Exon 4 of 10	ENSP00000356311.5	A0A8V8N8P9
	INAVA	ENST00000877560.1		c.255C>T	p.Ile85Ile	synonymous	Exon 4 of 10	ENSP00000547619.1

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 158 AN: 152222 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00137

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00104 AC: 260 AN: 251074 AF XY: 0.00104

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.00705

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000943

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00109 AC: 1594 AN: 1461800 Hom.: 4 Cov.: 31 AF XY: 0.00112 AC XY: 816 AN XY: 727212

African (AFR) AF: 0.000896 AC: 30 AN: 33480

American (AMR) AF: 0.00174 AC: 78 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00846 AC: 221 AN: 26130

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000325 AC: 28 AN: 86254

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53418

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5766

European-Non Finnish (NFE) AF: 0.000982 AC: 1092 AN: 1111952

Other (OTH) AF: 0.00197 AC: 119 AN: 60388

GnomAD4 genome AF: 0.00104 AC: 158 AN: 152340 Hom.: 0 Cov.: 33 AF XY: 0.00110 AC XY: 82 AN XY: 74488

African (AFR) AF: 0.000216 AC: 9 AN: 41588

American (AMR) AF: 0.00111 AC: 17 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00137 AC: 93 AN: 68022

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00146 Hom.: 0

Bravo AF: 0.000994

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00251

EpiControl AF: 0.00190

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.70
DANN	Benign	0.89
PhyloP100		-1.7
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs34596202; hg19: chr1-200869306; COSMIC: COSV66257330; COSMIC: COSV66257330;