Variant rs11790431 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014425.5(INVS):c.2068+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,604,612 control chromosomes in the GnomAD database, including 20,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3124 hom., cov: 33)

Exomes 𝑓: 0.15 ( 17325 hom. )

Consequence

INVS
NM_014425.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.425

Variant links:

Genes affected

INVS (HGNC:17870): (inversin) This gene encodes a protein containing multiple ankyrin domains and two IQ calmodulin-binding domains. The encoded protein may function in renal tubular development and function, and in left-right axis determination. This protein interacts with nephrocystin and infers a connection between primary cilia function and left-right axis determination. A similar protein in mice interacts with calmodulin. Mutations in this gene have been associated with nephronophthisis type 2. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2012]

INVS links:

INVS (HGNC:):

INVS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 9-100284634-G-A is Benign according to our data. Variant chr9-100284634-G-A is described in ClinVar as [Benign]. Clinvar id is 260409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
INVS	NM_014425.5 linkuse as main transcript	c.2068+31G>A	intron_variant	ENST00000262457.7	NP_055240.2	Q9Y283-1A0A024R153
INVS	NM_001318381.2 linkuse as main transcript	c.1780+31G>A	intron_variant		NP_001305310.1	Q2M1I4
INVS	NM_001318382.2 linkuse as main transcript	c.1090+31G>A	intron_variant		NP_001305311.1
INVS	NR_134606.2 linkuse as main transcript	n.2266+31G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INVS	ENST00000262457.7 linkuse as main transcript	c.2068+31G>A		intron_variant		1	NM_014425.5	ENSP00000262457.2		Q9Y283-1
INVS	ENST00000262456.6 linkuse as main transcript	c.2068+31G>A		intron_variant		5		ENSP00000262456.2		Q9Y283-2

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

28009

AN:

152048

Hom.:

3122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.315

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.0600

Gnomad EAS

AF:

0.00866

Gnomad SAS

AF:

0.0648

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.159

GnomAD3 exomes

AF:

0.125

AC:

29427

AN:

235816

Hom.:

2323

AF XY:

0.122

AC XY:

15604

AN XY:

128074

show subpopulations

Gnomad AFR exome

AF:

0.311

Gnomad AMR exome

AF:

0.0767

Gnomad ASJ exome

AF:

0.0626

Gnomad EAS exome

AF:

0.00778

Gnomad SAS exome

AF:

0.0677

Gnomad FIN exome

AF:

0.147

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.147

AC:

213025

AN:

1452446

Hom.:

17325

Cov.:

AF XY:

0.144

AC XY:

103691

AN XY:

722038

show subpopulations

Gnomad4 AFR exome

AF:

0.317

Gnomad4 AMR exome

AF:

0.0834

Gnomad4 ASJ exome

AF:

0.0629

Gnomad4 EAS exome

AF:

0.0114

Gnomad4 SAS exome

AF:

0.0705

Gnomad4 FIN exome

AF:

0.142

Gnomad4 NFE exome

AF:

0.157

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.184

AC:

28035

AN:

152166

Hom.:

3124

Cov.:

AF XY:

0.179

AC XY:

13306

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.315

Gnomad4 AMR

AF:

0.135

Gnomad4 ASJ

AF:

0.0600

Gnomad4 EAS

AF:

0.00868

Gnomad4 SAS

AF:

0.0642

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.151

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.129

Hom.:

857

Bravo

AF:

0.187

Asia WGS

AF:

0.0510

AC:

181

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.48

DANN

Benign

0.34

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