rs11790431

Variant names:

• chr9-100284634-G-A
• rs11790431
• NM_014425.5:c.2068+31G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-100284634-G-A
• chr9-100284634-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.425
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• nephronophthisis 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• Senior-Loken syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INVS	NM_014425.5	c.2068+31G>A		intron_variant	Intron 13 of 16	ENST00000262457.7	NP_055240.2
INVS	NM_001318381.2	c.1780+31G>A		intron_variant	Intron 14 of 17		NP_001305310.1
INVS	NM_001318382.2	c.1090+31G>A		intron_variant	Intron 13 of 16		NP_001305311.1
INVS	NR_134606.2	n.2266+31G>A		intron_variant	Intron 13 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INVS	ENST00000262457.7	c.2068+31G>A		intron_variant	Intron 13 of 16	1	NM_014425.5	ENSP00000262457.2
INVS	ENST00000262456.6	c.2068+31G>A		intron_variant	Intron 13 of 17	5		ENSP00000262456.2

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28009 AN: 152048 Hom.: 3122 Cov.: 33

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

GnomAD2 exomes AF: 0.125 AC: 29427 AN: 235816 AF XY: 0.122

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 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.: 31 AF XY: 0.144 AC XY: 103691 AN XY: 722038

African (AFR) AF: 0.317 AC: 10546 AN: 33306

American (AMR) AF: 0.0834 AC: 3676 AN: 44098

Ashkenazi Jewish (ASJ) AF: 0.0629 AC: 1629 AN: 25898

East Asian (EAS) AF: 0.0114 AC: 450 AN: 39606

South Asian (SAS) AF: 0.0705 AC: 6004 AN: 85194

European-Finnish (FIN) AF: 0.142 AC: 7491 AN: 52926

Middle Eastern (MID) AF: 0.123 AC: 602 AN: 4880

European-Non Finnish (NFE) AF: 0.157 AC: 173807 AN: 1106596

Other (OTH) AF: 0.147 AC: 8820 AN: 59942

GnomAD4 genome AF: 0.184 AC: 28035 AN: 152166 Hom.: 3124 Cov.: 33 AF XY: 0.179 AC XY: 13306 AN XY: 74390

African (AFR) AF: 0.315 AC: 13053 AN: 41482

American (AMR) AF: 0.135 AC: 2067 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0600 AC: 208 AN: 3468

East Asian (EAS) AF: 0.00868 AC: 45 AN: 5184

South Asian (SAS) AF: 0.0642 AC: 310 AN: 4826

European-Finnish (FIN) AF: 0.151 AC: 1595 AN: 10594

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10284 AN: 67998

Other (OTH) AF: 0.157 AC: 332 AN: 2116

Alfa AF: 0.132 Hom.: 1000

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.34
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11790431; hg19: chr9-103046916;