1-200912264-C-T

Position:

• chr1-200912264-C-T

Variant summary

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

The NM_001142569.3(INAVA):​c.1644+127C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 931,772 control chromosomes in the GnomAD database, including 47,603 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 0.32 (8264 hom., cov: 32)
  • Exomes 𝑓: 0.31 (39339 hom.)
• Consequence: INAVA NM_001142569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INAVA	NM_001142569.3	c.1644+127C>T		intron_variant		ENST00000413687.3	NP_001136041.1
INAVA	NM_001367289.1	c.1584+187C>T		intron_variant			NP_001354218.1
INAVA	NM_001367290.1	c.1107+127C>T		intron_variant			NP_001354219.1
INAVA	NM_018265.4	c.1899+127C>T		intron_variant			NP_060735.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INAVA	ENST00000413687.3	c.1644+127C>T		intron_variant		2	NM_001142569.3	ENSP00000392105	P2
INAVA	ENST00000367342.8	c.1941+127C>T		intron_variant		1		ENSP00000356311	A2
INAVA	ENST00000465162.1	n.179+127C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48762 AN: 151882 Hom.: 8258 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.308 AC: 240549 AN: 779772 Hom.: 39339 AF XY: 0.313 AC XY: 122290 AN XY: 390328

Gnomad4 AFR exome AF: 0.406

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.276

Gnomad4 EAS exome AF: 0.231

Gnomad4 SAS exome AF: 0.455

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.321 AC: 48800 AN: 152000 Hom.: 8264 Cov.: 32 AF XY: 0.319 AC XY: 23703 AN XY: 74290

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.281

Alfa AF: 0.302 Hom.: 2220

Bravo AF: 0.320

Asia WGS AF: 0.347 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.9
DANN	Benign	0.79

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: rs10800746; hg19: chr1-200881392;