Variant 9-100297194-A-G 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.3016+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 1,399,296 control chromosomes in the GnomAD database, including 285,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34892 hom., cov: 32)

Exomes 𝑓: 0.63 ( 250849 hom. )

Consequence

INVS
NM_014425.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.242

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:

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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=-0.85).

BP6

Variant 9-100297194-A-G is Benign according to our data. Variant chr9-100297194-A-G is described in ClinVar as [Benign]. Clinvar id is 260414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
INVS	NM_014425.5 link	c.3016+48A>G	intron_variant	ENST00000262457.7	NP_055240.2	Q9Y283-1A0A024R153
INVS	NM_001318381.2 link	c.2728+48A>G	intron_variant		NP_001305310.1	Q2M1I4
INVS	NM_001318382.2 link	c.2038+48A>G	intron_variant		NP_001305311.1
INVS	NR_134606.2 link	n.3165+48A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INVS	ENST00000262457.7 link	c.3016+48A>G		intron_variant		1	NM_014425.5	ENSP00000262457.2		Q9Y283-1
INVS	ENST00000262456.6 link	c.2506+48A>G		intron_variant		5		ENSP00000262456.2		Q9Y283-2

Frequencies

GnomAD3 genomes

AF:

0.671

AC:

102015

AN:

151952

Hom.:

34874

Cov.:

show subpopulations

Gnomad AFR

AF:

0.757

Gnomad AMI

AF:

0.381

Gnomad AMR

AF:

0.727

Gnomad ASJ

AF:

0.668

Gnomad EAS

AF:

0.895

Gnomad SAS

AF:

0.784

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.671

Gnomad NFE

AF:

0.590

Gnomad OTH

AF:

0.655

GnomAD3 exomes

AF:

0.686

AC:

156491

AN:

227998

Hom.:

54918

AF XY:

0.681

AC XY:

84000

AN XY:

123278

show subpopulations

Gnomad AFR exome

AF:

0.762

Gnomad AMR exome

AF:

0.819

Gnomad ASJ exome

AF:

0.654

Gnomad EAS exome

AF:

0.896

Gnomad SAS exome

AF:

0.775

Gnomad FIN exome

AF:

0.639

Gnomad NFE exome

AF:

0.589

Gnomad OTH exome

AF:

0.644

GnomAD4 exome

AF:

0.628

AC:

782741

AN:

1247226

Hom.:

250849

Cov.:

AF XY:

0.630

AC XY:

396999

AN XY:

629986

show subpopulations

Gnomad4 AFR exome

AF:

0.761

Gnomad4 AMR exome

AF:

0.809

Gnomad4 ASJ exome

AF:

0.653

Gnomad4 EAS exome

AF:

0.919

Gnomad4 SAS exome

AF:

0.771

Gnomad4 FIN exome

AF:

0.629

Gnomad4 NFE exome

AF:

0.588

Gnomad4 OTH exome

AF:

0.648

GnomAD4 genome

AF:

0.671

AC:

102088

AN:

152070

Hom.:

34892

Cov.:

AF XY:

0.678

AC XY:

50427

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.756

Gnomad4 AMR

AF:

0.727

Gnomad4 ASJ

AF:

0.668

Gnomad4 EAS

AF:

0.895

Gnomad4 SAS

AF:

0.783

Gnomad4 FIN

AF:

0.652

Gnomad4 NFE

AF:

0.590

Gnomad4 OTH

AF:

0.653

Alfa

AF:

0.605

Hom.:

4718

Bravo

AF:

0.679

Asia WGS

AF:

0.791

AC:

2751

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

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

-0.85

CADD

Benign

9.4

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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