NM_001142569.3:c.1644+127C>A

Variant names:

• chr1-200912264-C-A
• rs10800746
• NM_001142569.3:c.1644+127C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142569.3(INAVA):​c.1644+127C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 780,946 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: INAVA NM_001142569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INAVA	NM_001142569.3	c.1644+127C>A		intron_variant	Intron 9 of 9	ENST00000413687.3	NP_001136041.1
INAVA	NM_018265.4	c.1899+127C>A		intron_variant	Intron 9 of 9		NP_060735.4
INAVA	NM_001367289.1	c.1584+187C>A		intron_variant	Intron 9 of 9		NP_001354218.1
INAVA	NM_001367290.1	c.1107+127C>A		intron_variant	Intron 9 of 9		NP_001354219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INAVA	ENST00000413687.3	c.1644+127C>A		intron_variant	Intron 9 of 9	2	NM_001142569.3	ENSP00000392105.2
INAVA	ENST00000367342.8	c.1941+127C>A		intron_variant	Intron 9 of 9	1		ENSP00000356311.5
INAVA	ENST00000465162.1	n.179+127C>A		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000128 AC: 1 AN: 780946 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 390928

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18184

American (AMR) AF: 0.00 AC: 0 AN: 17814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15404

East Asian (EAS) AF: 0.00 AC: 0 AN: 31386

South Asian (SAS) AF: 0.00 AC: 0 AN: 51870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3072

European-Non Finnish (NFE) AF: 0.00000173 AC: 1 AN: 576460

Other (OTH) AF: 0.00 AC: 0 AN: 37054

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.82
PhyloP100		-0.29

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: rs10800746; hg19: chr1-200881392;