Variant 3-190322667-G-A 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 XM_047447333.1(CLDN16):c.-170+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 231,914 control chromosomes in the GnomAD database, including 1,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 988 hom., cov: 32)

Exomes 𝑓: 0.11 ( 570 hom. )

Consequence

CLDN16
XM_047447333.1 splice_donor_region, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.56

Variant links:

Genes affected

CLDN16 (HGNC:2037): (claudin 16) Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The protein encoded by this gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. It is found primarily in the kidneys, specifically in the thick ascending limb of Henle, where it acts as either an intercellular pore or ion concentration sensor to regulate the paracellular resorption of magnesium ions. Defects in this gene are a cause of primary hypomagnesemia, which is characterized by massive renal magnesium wasting with hypomagnesemia and hypercalciuria, resulting in nephrocalcinosis and renal failure. This gene and the CLDN1 gene are clustered on chromosome 3q28. [provided by RefSeq, Jun 2010]

CLDN16 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 3-190322667-G-A is Benign according to our data. Variant chr3-190322667-G-A is described in ClinVar as [Benign]. Clinvar id is 1267401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect
CLDN16	NM_001378492.1 linkuse as main transcript	c.-279+7608G>A	intron_variant
CLDN16	NM_001378493.1 linkuse as main transcript	c.-279+32076G>A	intron_variant
CLDN16	XM_047447333.1 linkuse as main transcript	c.-170+6G>A	splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN16	ENST00000468220.1 linkuse as main transcript	n.121+6G>A		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15798

AN:

152150

Hom.:

985

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.0628

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0774

Gnomad OTH

AF:

0.124

GnomAD4 exome

AF:

0.107

AC:

8557

AN:

79646

Hom.:

570

Cov.:

AF XY:

0.117

AC XY:

4836

AN XY:

41352

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.179

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.215

Gnomad4 SAS exome

AF:

0.181

Gnomad4 FIN exome

AF:

0.0705

Gnomad4 NFE exome

AF:

0.0839

Gnomad4 OTH exome

AF:

0.0897

GnomAD4 genome

AF:

0.104

AC:

15832

AN:

152268

Hom.:

988

Cov.:

AF XY:

0.107

AC XY:

7997

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.114

Gnomad4 AMR

AF:

0.162

Gnomad4 ASJ

AF:

0.105

Gnomad4 EAS

AF:

0.224

Gnomad4 SAS

AF:

0.177

Gnomad4 FIN

AF:

0.0628

Gnomad4 NFE

AF:

0.0775

Gnomad4 OTH

AF:

0.126

Alfa

AF:

0.0848

Hom.:

Bravo

AF:

0.111

Asia WGS

AF:

0.198

AC:

687

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.98

DANN

Benign

0.83

Splicing

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