rs7554511

Variant names:

• chr1-200908434-C-A
• rs7554511
• NM_001142569.3:c.575-296C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 84 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INAVA	NM_001142569.3	MANE Select	c.575-296C>A		intron	N/A	NP_001136041.1	Q3KP66-3
	INAVA	NM_018265.4		c.830-296C>A		intron	N/A	NP_060735.4	Q3KP66-1
	INAVA	NM_001367289.1		c.575-296C>A		intron	N/A	NP_001354218.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INAVA	ENST00000413687.3	TSL:2 MANE Select	c.575-296C>A		intron	N/A	ENSP00000392105.2	Q3KP66-3
	INAVA	ENST00000367342.8	TSL:1	c.872-296C>A		intron	N/A	ENSP00000356311.5	A0A8V8N8P9
	INAVA	ENST00000877560.1		c.575-296C>A		intron	N/A	ENSP00000547619.1

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

African (AFR) AF: 0.160 AC: 725 AN: 4542

American (AMR) AF: 0.137 AC: 719 AN: 5266

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 1212 AN: 5542

East Asian (EAS) AF: 0.0207 AC: 219 AN: 10586

South Asian (SAS) AF: 0.131 AC: 749 AN: 5704

European-Finnish (FIN) AF: 0.196 AC: 1910 AN: 9732

Middle Eastern (MID) AF: 0.187 AC: 144 AN: 772

European-Non Finnish (NFE) AF: 0.261 AC: 24938 AN: 95580

Other (OTH) AF: 0.210 AC: 2080 AN: 9900

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

African (AFR) AF: 0.165 AC: 6860 AN: 41524

American (AMR) AF: 0.156 AC: 2384 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 791 AN: 3468

East Asian (EAS) AF: 0.00560 AC: 29 AN: 5180

South Asian (SAS) AF: 0.140 AC: 674 AN: 4828

European-Finnish (FIN) AF: 0.194 AC: 2052 AN: 10586

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18776 AN: 67972

Other (OTH) AF: 0.194 AC: 411 AN: 2116

Alfa AF: 0.249 Hom.: 20109

Bravo AF: 0.208

Asia WGS AF: 0.0770 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.4
DANN	Benign	0.62
PhyloP100		0.11
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7554511;

hg19: chr1-200877562;