Variant rs41274951 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.2787-23C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,589,220 control chromosomes in the GnomAD database, including 16,885 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1400 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15485 hom. )

Consequence

INVS
NM_014425.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0350

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 9-100296894-C-G is Benign according to our data. Variant chr9-100296894-C-G is described in ClinVar as [Benign]. Clinvar id is 260413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
INVS	NM_014425.5 link	c.2787-23C>G	intron_variant	ENST00000262457.7	NP_055240.2	Q9Y283-1A0A024R153
INVS	NM_001318381.2 link	c.2499-23C>G	intron_variant		NP_001305310.1	Q2M1I4
INVS	NM_001318382.2 link	c.1809-23C>G	intron_variant		NP_001305311.1
INVS	NR_134606.2 link	n.2936-23C>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INVS	ENST00000262457.7 link	c.2787-23C>G		intron_variant		1	NM_014425.5	ENSP00000262457.2		Q9Y283-1
INVS	ENST00000262456.6 link	c.2277-23C>G		intron_variant		5		ENSP00000262456.2		Q9Y283-2

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20177

AN:

152050

Hom.:

1402

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.0678

Gnomad EAS

AF:

0.000966

Gnomad SAS

AF:

0.0616

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.121

GnomAD3 exomes

AF:

0.113

AC:

28143

AN:

249686

Hom.:

1849

AF XY:

0.113

AC XY:

15226

AN XY:

134818

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.0678

Gnomad ASJ exome

AF:

0.0698

Gnomad EAS exome

AF:

0.000491

Gnomad SAS exome

AF:

0.0656

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.151

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.141

AC:

202549

AN:

1437052

Hom.:

15485

Cov.:

AF XY:

0.139

AC XY:

99303

AN XY:

716346

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.0732

Gnomad4 ASJ exome

AF:

0.0704

Gnomad4 EAS exome

AF:

0.000303

Gnomad4 SAS exome

AF:

0.0683

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.157

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.133

AC:

20191

AN:

152168

Hom.:

1400

Cov.:

AF XY:

0.129

AC XY:

9590

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.136

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.0678

Gnomad4 EAS

AF:

0.000969

Gnomad4 SAS

AF:

0.0614

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.151

Gnomad4 OTH

AF:

0.119

Alfa

AF:

0.133

Hom.:

247

Bravo

AF:

0.130

Asia WGS

AF:

0.0360

AC:

128

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

-0.72

CADD

Benign

2.9

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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