rs41274951

chr9-100296894-C-G

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0350

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=-0.72).
• 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	HGVSp	Effect	#exon/exons	MANE	UniProt
INVS	NM_014425.5	c.2787-23C>G		intron_variant		ENST00000262457.7
INVS	NM_001318381.2	c.2499-23C>G		intron_variant
INVS	NM_001318382.2	c.1809-23C>G		intron_variant
INVS	NR_134606.2	n.2936-23C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INVS	ENST00000262457.7	c.2787-23C>G		intron_variant		1	NM_014425.5	A2
INVS	ENST00000262456.6	c.2277-23C>G		intron_variant		5		P4

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20177 AN: 152050 Hom.: 1402 Cov.: 32

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

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.: 28 AF XY: 0.139 AC XY: 99303 AN XY: 716346

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.: 32 AF XY: 0.129 AC XY: 9590 AN XY: 74384

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: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	-0.72
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

Other links and lift over

dbSNP: rs41274951; hg19: chr9-103059176;