chr1-200912467-G-A

Variant names:

• chr1-200912467-G-A
• rs7522462
• NM_001142569.3:c.1644+330G>A

Variant summary

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

The NM_018265.4(INAVA):​c.1899+330G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,062 control chromosomes in the GnomAD database, including 3,669 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 (3669 hom., cov: 31)
• Consequence: INAVA NM_018265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753
• Publications: 57 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=-0.9).
• 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_018265.4. 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.1644+330G>A		intron	N/A	NP_001136041.1
	INAVA	NM_018265.4		c.1899+330G>A		intron	N/A	NP_060735.4
	INAVA	NM_001367289.1		c.1584+390G>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.1644+330G>A		intron	N/A	ENSP00000392105.2
	INAVA	ENST00000367342.8	TSL:1	c.1941+330G>A		intron	N/A	ENSP00000356311.5
	INAVA	ENST00000877560.1		c.1644+330G>A		intron	N/A	ENSP00000547619.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31345 AN: 151944 Hom.: 3668 Cov.: 31

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.206 AC: 31345 AN: 152062 Hom.: 3669 Cov.: 31 AF XY: 0.200 AC XY: 14859 AN XY: 74310

African (AFR) AF: 0.139 AC: 5775 AN: 41480

American (AMR) AF: 0.155 AC: 2361 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 804 AN: 3470

East Asian (EAS) AF: 0.00483 AC: 25 AN: 5176

South Asian (SAS) AF: 0.144 AC: 696 AN: 4826

European-Finnish (FIN) AF: 0.194 AC: 2047 AN: 10576

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18760 AN: 67950

Other (OTH) AF: 0.191 AC: 403 AN: 2108

Alfa AF: 0.246 Hom.: 15693

Bravo AF: 0.200

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	-0.90
CADD	Benign	0.45
DANN	Benign	0.31
PhyloP100		-0.75
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: rs7522462; hg19: chr1-200881595;