Variant 1-185298054-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_006469.5(IVNS1ABP):c.1910C>T(p.Thr637Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

IVNS1ABP
NM_006469.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45

Variant links:

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]

IVNS1ABP links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, IVNS1ABP

BP4

Computational evidence support a benign effect (MetaRNN=0.11741528).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IVNS1ABP	NM_006469.5 linkuse as main transcript	c.1910C>T	p.Thr637Ile	missense_variant	15/15	ENST00000367498.8
IVNS1ABP	XM_047434070.1 linkuse as main transcript	c.1910C>T	p.Thr637Ile	missense_variant	15/15
IVNS1ABP	XM_047434096.1 linkuse as main transcript	c.1643C>T	p.Thr548Ile	missense_variant	14/14
IVNS1ABP	XM_047434109.1 linkuse as main transcript	c.1256C>T	p.Thr419Ile	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
IVNS1ABP	ENST00000367498.8 linkuse as main transcript	c.1910C>T	p.Thr637Ile	missense_variant	15/15	1	NM_006469.5	P1
IVNS1ABP	ENST00000480769.5 linkuse as main transcript	n.2110C>T		non_coding_transcript_exon_variant	8/8	1
IVNS1ABP	ENST00000459929.5 linkuse as main transcript	n.2618C>T		non_coding_transcript_exon_variant	16/16	5
IVNS1ABP	ENST00000475046.5 linkuse as main transcript	n.1533C>T		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250736

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135538

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461198

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.1910C>T (p.T637I) alteration is located in exon 15 (coding exon 13) of the IVNS1ABP gene. This alteration results from a C to T substitution at nucleotide position 1910, causing the threonine (T) at amino acid position 637 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.17

Eigen

Benign

-0.091

Eigen_PC

Benign

0.083

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.82

M_CAP

Benign

0.046

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.14

REVEL

Benign

0.21

Sift

Benign

0.12

Sift4G

Uncertain

0.013

Polyphen

0.0010

Vest4

0.093

MutPred

0.52

Loss of disorder (P = 0.0214);

MVP

0.55

MPC

0.52

ClinPred

0.29

GERP RS

4.5

Varity_R

0.14

gMVP

0.30

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over