1-185298065-C-T

Position:

• chr1-185298065-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_Moderate PM2 PP5

The NM_006469.5(IVNS1ABP):​c.1899G>A​(p.Trp633Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IVNS1ABP NM_006469.5 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.70

Genes affected

IVNS1ABP (HGNC:16951): (influenza virus NS1A binding protein) Involved in RNA splicing; negative regulation of protein ubiquitination; and response to virus. Located in cytosol. Implicated in immunodeficiency 70. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0156 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-185298065-C-T is Pathogenic according to our data. Variant chr1-185298065-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 974684.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IVNS1ABP	NM_006469.5	c.1899G>A	p.Trp633Ter	stop_gained	15/15	ENST00000367498.8
IVNS1ABP	XM_047434070.1	c.1899G>A	p.Trp633Ter	stop_gained	15/15
IVNS1ABP	XM_047434096.1	c.1632G>A	p.Trp544Ter	stop_gained	14/14
IVNS1ABP	XM_047434109.1	c.1245G>A	p.Trp415Ter	stop_gained	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IVNS1ABP	ENST00000367498.8	c.1899G>A	p.Trp633Ter	stop_gained	15/15	1	NM_006469.5	P1
IVNS1ABP	ENST00000480769.5	n.2099G>A		non_coding_transcript_exon_variant	8/8	1
IVNS1ABP	ENST00000459929.5	n.2607G>A		non_coding_transcript_exon_variant	16/16	5
IVNS1ABP	ENST00000475046.5	n.1522G>A		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Immunodeficiency 70 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 31, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.66
CADD	Pathogenic	39
DANN	Uncertain	0.99
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
MutationTaster	Benign	1.0	D;D
Vest4		0.40
GERP RS		5.4

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: rs1665467187; hg19: chr1-185267197;