rs4915463

Variant names:

• chr1-200910174-A-G
• rs4915463
• NM_001142569.3:c.959+777A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-200910174-A-G
• chr1-200910174-A-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.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
• Publications: 8 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INAVA	NM_001142569.3	MANE Select	c.959+777A>G		intron	N/A	NP_001136041.1
	INAVA	NM_018265.4		c.1214+777A>G		intron	N/A	NP_060735.4
	INAVA	NM_001367289.1		c.959+777A>G		intron	N/A	NP_001354218.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INAVA	ENST00000413687.3	TSL:2 MANE Select	c.959+777A>G		intron	N/A	ENSP00000392105.2
	INAVA	ENST00000367342.8	TSL:1	c.1256+777A>G		intron	N/A	ENSP00000356311.5
	INAVA	ENST00000526172.1	TSL:4	n.440+777A>G		intron	N/A

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

African (AFR) AF: 0.413 AC: 17112 AN: 41448

American (AMR) AF: 0.573 AC: 8749 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2210 AN: 3470

East Asian (EAS) AF: 0.142 AC: 734 AN: 5178

South Asian (SAS) AF: 0.403 AC: 1944 AN: 4822

European-Finnish (FIN) AF: 0.507 AC: 5351 AN: 10560

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41414 AN: 67962

Other (OTH) AF: 0.535 AC: 1130 AN: 2112

Alfa AF: 0.566 Hom.: 12929

Bravo AF: 0.524

Asia WGS AF: 0.278 AC: 972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.32
DANN	Benign	0.36
PhyloP100		-0.83
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: rs4915463; hg19: chr1-200879302;