rs4915463

Positions:

• chr1-200910174-A-G
• chr1-200910174-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142569.3(INAVA):​c.959+777A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,020 control chromosomes in the GnomAD database, including 21,830 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 0.52 (21830 hom., cov: 32)
• Consequence: INAVA NM_001142569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.832

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INAVA	NM_001142569.3	c.959+777A>G		intron_variant		ENST00000413687.3	NP_001136041.1
INAVA	NM_001367289.1	c.959+777A>G		intron_variant			NP_001354218.1
INAVA	NM_001367290.1	c.422+777A>G		intron_variant			NP_001354219.1
INAVA	NM_018265.4	c.1214+777A>G		intron_variant			NP_060735.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INAVA	ENST00000413687.3	c.959+777A>G		intron_variant		2	NM_001142569.3	ENSP00000392105	P2
INAVA	ENST00000367342.8	c.1256+777A>G		intron_variant		1		ENSP00000356311	A2
INAVA	ENST00000526172.1	n.440+777A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79481 AN: 151902 Hom.: 21821 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.523 AC: 79521 AN: 152020 Hom.: 21830 Cov.: 32 AF XY: 0.518 AC XY: 38470 AN XY: 74322

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.535

Alfa AF: 0.561 Hom.: 11506

Bravo AF: 0.524

Asia WGS AF: 0.278 AC: 972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.32
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs4915463; hg19: chr1-200879302;