chr1-200911898-C-T

Variant names:

• chr1-200911898-C-T
• rs61745433
• NM_001142569.3:c.1405C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001142569.3(INAVA):​c.1405C>T​(p.Arg469Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,581,504 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 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.982
• 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0074567795).
• BP6: Variant 1-200911898-C-T is Benign according to our data. Variant chr1-200911898-C-T is described in ClinVar as Benign. ClinVar VariationId is 781799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.1405C>T	p.Arg469Cys	missense	Exon 9 of 10	NP_001136041.1	Q3KP66-3
	INAVA	NM_018265.4		c.1660C>T	p.Arg554Cys	missense	Exon 9 of 10	NP_060735.4	Q3KP66-1
	INAVA	NM_001367289.1		c.1405C>T	p.Arg469Cys	missense	Exon 9 of 10	NP_001354218.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INAVA	ENST00000413687.3	TSL:2 MANE Select	c.1405C>T	p.Arg469Cys	missense	Exon 9 of 10	ENSP00000392105.2	Q3KP66-3
	INAVA	ENST00000367342.8	TSL:1	c.1702C>T	p.Arg568Cys	missense	Exon 9 of 10	ENSP00000356311.5	A0A8V8N8P9
	INAVA	ENST00000877560.1		c.1405C>T	p.Arg469Cys	missense	Exon 9 of 10	ENSP00000547619.1

Frequencies

GnomAD3 genomes AF: 0.00102 AC: 155 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00135

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00111 AC: 217 AN: 195798 AF XY: 0.00108

Gnomad AFR exome AF: 0.000268

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00721

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00101

Gnomad OTH exome AF: 0.00316

GnomAD4 exome AF: 0.00110 AC: 1571 AN: 1429148 Hom.: 4 Cov.: 38 AF XY: 0.00114 AC XY: 810 AN XY: 709930

African (AFR) AF: 0.000850 AC: 28 AN: 32940

American (AMR) AF: 0.00177 AC: 74 AN: 41698

Ashkenazi Jewish (ASJ) AF: 0.00849 AC: 218 AN: 25664

East Asian (EAS) AF: 0.00 AC: 0 AN: 38336

South Asian (SAS) AF: 0.000179 AC: 15 AN: 83750

European-Finnish (FIN) AF: 0.0000502 AC: 2 AN: 39816

Middle Eastern (MID) AF: 0.00455 AC: 19 AN: 4172

European-Non Finnish (NFE) AF: 0.000995 AC: 1098 AN: 1103500

Other (OTH) AF: 0.00197 AC: 117 AN: 59272

GnomAD4 genome AF: 0.00102 AC: 155 AN: 152356 Hom.: 0 Cov.: 33 AF XY: 0.00109 AC XY: 81 AN XY: 74502

African (AFR) AF: 0.000216 AC: 9 AN: 41584

American (AMR) AF: 0.00118 AC: 18 AN: 15314

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00135 AC: 92 AN: 68024

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

Alfa AF: 0.00170 Hom.: 0

Bravo AF: 0.000979

ExAC AF: 0.000912 AC: 106

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
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.0075	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.98
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.15
Sift	Benign	0.041	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.047	B
Vest4		0.39
MVP		0.12
MPC		2.3
ClinPred		0.025	T
GERP RS		4.4
Varity_R		0.14
gMVP		0.70
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs61745433; hg19: chr1-200881026; COSMIC: COSV100949868; COSMIC: COSV100949868;