Genetic Variant NM_014425.5:c.274-15_274-14delTT (chr9-100226046-CTT-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_014425.5(INVS):c.274-15_274-14delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,598,052 control chromosomes in the GnomAD database, including 13,730 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3603 hom., cov: 28)

Exomes 𝑓: 0.11 ( 10127 hom. )

Consequence

INVS
NM_014425.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.960

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 -16 ACMG points.

BP6

Variant 9-100226046-CTT-C is Benign according to our data. Variant chr9-100226046-CTT-C is described in ClinVar as [Benign]. Clinvar id is 260412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-100226046-CTT-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
INVS	NM_014425.5 link	c.274-15_274-14delTT	intron_variant	Intron 3 of 16	ENST00000262457.7	NP_055240.2	Q9Y283-1A0A024R153
INVS	NM_001318381.2 link	c.-15-15_-15-14delTT	intron_variant	Intron 4 of 17		NP_001305310.1	Q2M1I4
INVS	NM_001318382.2 link	c.-716-15_-716-14delTT	intron_variant	Intron 3 of 16		NP_001305311.1
INVS	NR_134606.2 link	n.472-15_472-14delTT	intron_variant	Intron 3 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INVS	ENST00000262457.7 link	c.274-15_274-14delTT		intron_variant	Intron 3 of 16	1	NM_014425.5	ENSP00000262457.2		Q9Y283-1

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26828

AN:

151838

Hom.:

3592

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.100

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.0452

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.0427

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.102

AC:

23843

AN:

234502

Hom.:

1942

AF XY:

0.0961

AC XY:

12174

AN XY:

126684

show subpopulations

Gnomad AFR exome

AF:

0.379

Gnomad AMR exome

AF:

0.0576

Gnomad ASJ exome

AF:

0.0477

Gnomad EAS exome

AF:

0.00131

Gnomad SAS exome

AF:

0.0402

Gnomad FIN exome

AF:

0.144

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.0955

GnomAD4 exome

AF:

0.106

AC:

153033

AN:

1446096

Hom.:

10127

AF XY:

0.103

AC XY:

73845

AN XY:

718658

show subpopulations

Gnomad4 AFR exome

AF:

0.388

Gnomad4 AMR exome

AF:

0.0637

Gnomad4 ASJ exome

AF:

0.0464

Gnomad4 EAS exome

AF:

0.000885

Gnomad4 SAS exome

AF:

0.0433

Gnomad4 FIN exome

AF:

0.136

Gnomad4 NFE exome

AF:

0.107

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.177

AC:

26876

AN:

151956

Hom.:

3603

Cov.:

AF XY:

0.173

AC XY:

12878

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.383

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.0452

Gnomad4 EAS

AF:

0.00366

Gnomad4 SAS

AF:

0.0421

Gnomad4 FIN

AF:

0.145

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.129

Hom.:

342

Bravo

AF:

0.182

Asia WGS

AF:

0.0460

AC:

162

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nephronophthisis

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Sep 06, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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