rs296533

Variant names:

• chr1-200896640-G-T
• rs296533
• NM_001142569.3:c.-95+1553G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142569.3(INAVA):​c.-95+1553G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,248 control chromosomes in the GnomAD database, including 5,625 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5625 hom., cov: 33)
• Consequence: INAVA NM_001142569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INAVA	NM_001142569.3	c.-95+1553G>T		intron_variant	Intron 1 of 9	ENST00000413687.3	NP_001136041.1
INAVA	NM_018265.4	c.162-1667G>T		intron_variant	Intron 1 of 9		NP_060735.4
INAVA	NM_001367289.1	c.-95+1553G>T		intron_variant	Intron 1 of 9		NP_001354218.1
INAVA	NM_001367290.1	c.-630+1553G>T		intron_variant	Intron 1 of 9		NP_001354219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INAVA	ENST00000413687.3	c.-95+1553G>T		intron_variant	Intron 1 of 9	2	NM_001142569.3	ENSP00000392105.2
INAVA	ENST00000367342.8	c.204-1667G>T		intron_variant	Intron 1 of 9	1		ENSP00000356311.5
INAVA	ENST00000451872.6	c.-9-1752G>T		intron_variant	Intron 1 of 4	3		ENSP00000397255.2
INAVA	ENST00000532631.5	c.-94-1667G>T		intron_variant	Intron 1 of 2	3		ENSP00000431682.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37747 AN: 152130 Hom.: 5623 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.243

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.248 AC: 37746 AN: 152248 Hom.: 5625 Cov.: 33 AF XY: 0.241 AC XY: 17939 AN XY: 74442

African (AFR) AF: 0.125 AC: 5203 AN: 41560

American (AMR) AF: 0.196 AC: 3006 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 966 AN: 3472

East Asian (EAS) AF: 0.0210 AC: 109 AN: 5184

South Asian (SAS) AF: 0.188 AC: 906 AN: 4826

European-Finnish (FIN) AF: 0.255 AC: 2699 AN: 10596

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23782 AN: 67988

Other (OTH) AF: 0.241 AC: 509 AN: 2114

Alfa AF: 0.312 Hom.: 24780

Bravo AF: 0.236

Asia WGS AF: 0.0870 AC: 306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.34
DANN	Benign	0.60
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs296533; hg19: chr1-200865768;