rs7554511

Positions:

• chr1-200908434-C-A

Variant summary

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

The NM_001142569.3(INAVA):​c.575-296C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 299,784 control chromosomes in the GnomAD database, including 8,028 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 0.21 (3833 hom., cov: 32)
  • Exomes 𝑓: 0.22 (4195 hom.)
• Consequence: INAVA NM_001142569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INAVA	NM_001142569.3	c.575-296C>A		intron_variant		ENST00000413687.3	NP_001136041.1
INAVA	NM_001367289.1	c.575-296C>A		intron_variant			NP_001354218.1
INAVA	NM_001367290.1	c.40-298C>A		intron_variant			NP_001354219.1
INAVA	NM_018265.4	c.830-296C>A		intron_variant			NP_060735.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INAVA	ENST00000413687.3	c.575-296C>A		intron_variant		2	NM_001142569.3	ENSP00000392105	P2
INAVA	ENST00000367342.8	c.872-296C>A		intron_variant		1		ENSP00000356311	A2

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32452 AN: 152042 Hom.: 3833 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.196

GnomAD4 exome AF: 0.221 AC: 32696 AN: 147624 Hom.: 4195 AF XY: 0.221 AC XY: 16548 AN XY: 74738

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.0207

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.213 AC: 32454 AN: 152160 Hom.: 3833 Cov.: 32 AF XY: 0.207 AC XY: 15379 AN XY: 74390

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.00560

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.194

Alfa AF: 0.249 Hom.: 9321

Bravo AF: 0.208

Asia WGS AF: 0.0770 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.4
DANN	Benign	0.62

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: rs7554511; hg19: chr1-200877562;