rs12118246

Variant names:

• chr1-200905719-C-A
• rs12118246
• NM_001142569.3:c.521-2115C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-200905719-C-A
• chr1-200905719-C-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.521-2115C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.089 in 152,248 control chromosomes in the GnomAD database, including 783 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 0.089 (783 hom., cov: 33)
• Consequence: INAVA NM_001142569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.626
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INAVA	NM_001142569.3	c.521-2115C>A		intron_variant	Intron 5 of 9	ENST00000413687.3	NP_001136041.1
INAVA	NM_018265.4	c.776-2115C>A		intron_variant	Intron 5 of 9		NP_060735.4
INAVA	NM_001367289.1	c.521-2115C>A		intron_variant	Intron 5 of 9		NP_001354218.1
INAVA	NM_001367290.1	c.-15-2115C>A		intron_variant	Intron 5 of 9		NP_001354219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INAVA	ENST00000413687.3	c.521-2115C>A		intron_variant	Intron 5 of 9	2	NM_001142569.3	ENSP00000392105.2
INAVA	ENST00000367342.8	c.818-2115C>A		intron_variant	Intron 5 of 9	1		ENSP00000356311.5
INAVA	ENST00000531649.1	n.150-473C>A		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.0891 AC: 13560 AN: 152130 Hom.: 783 Cov.: 33

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0710

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0779

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

GnomAD4 genome AF: 0.0890 AC: 13555 AN: 152248 Hom.: 783 Cov.: 33 AF XY: 0.0898 AC XY: 6688 AN XY: 74446

African (AFR) AF: 0.0283 AC: 1177 AN: 41554

American (AMR) AF: 0.0709 AC: 1085 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0680 AC: 236 AN: 3470

East Asian (EAS) AF: 0.109 AC: 567 AN: 5194

South Asian (SAS) AF: 0.0528 AC: 255 AN: 4828

European-Finnish (FIN) AF: 0.174 AC: 1837 AN: 10580

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8187 AN: 68002

Other (OTH) AF: 0.0766 AC: 162 AN: 2114

Alfa AF: 0.102 Hom.: 1104

Bravo AF: 0.0800

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.32
DANN	Benign	0.59
PhyloP100		-0.63
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: rs12118246; hg19: chr1-200874847;