rs11790431

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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:2
• Conservation: PhyloP100: -0.425

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
INVS	NM_014425.5	c.2068+31G>A		intron_variant		ENST00000262457.7
INVS	NM_001318381.2	c.1780+31G>A		intron_variant
INVS	NM_001318382.2	c.1090+31G>A		intron_variant
INVS	NR_134606.2	n.2266+31G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INVS	ENST00000262457.7	c.2068+31G>A		intron_variant		1	NM_014425.5	A2
INVS	ENST00000262456.6	c.2068+31G>A		intron_variant		5		P4

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

GnomAD3 exomes AF: 0.125 AC: 29427 AN: 235816 Hom.: 2323 AF XY: 0.122 AC XY: 15604 AN XY: 128074

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

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.: 33 AF XY: 0.179 AC XY: 13306 AN XY: 74390

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

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

Other links and lift over

dbSNP: rs11790431; hg19: chr9-103046916;