1-200912467-G-A

Position:

• chr1-200912467-G-A

Variant summary

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

The NM_001142569.3(INAVA):​c.1644+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_001142569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753

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=-0.9).
• 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.1644+330G>A		intron_variant		ENST00000413687.3	NP_001136041.1
INAVA	NM_001367289.1	c.1584+390G>A		intron_variant			NP_001354218.1
INAVA	NM_001367290.1	c.1107+330G>A		intron_variant			NP_001354219.1
INAVA	NM_018265.4	c.1899+330G>A		intron_variant			NP_060735.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INAVA	ENST00000413687.3	c.1644+330G>A		intron_variant		2	NM_001142569.3	ENSP00000392105	P2
INAVA	ENST00000367342.8	c.1941+330G>A		intron_variant		1		ENSP00000356311	A2
INAVA	ENST00000465162.1	n.179+330G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.00483

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.191

Alfa AF: 0.256 Hom.: 6914

Bravo AF: 0.200

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	-0.90
CADD	Benign	0.45
DANN	Benign	0.31

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: rs7522462; hg19: chr1-200881595;