rs9865730

Variant names:

• chr3-190387611-A-G
• rs9865730
• NM_001378492.1:c.-93-626A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-190387611-A-G
• chr3-190387611-A-C
• chr3-190387611-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378492.1(CLDN16):​c.-93-626A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.993 in 152,314 control chromosomes in the GnomAD database, including 75,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.99 (75070 hom., cov: 31)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.261
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• renal hypomagnesemia 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ENSG00000297357 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-190387611-A-G is Benign according to our data. Variant chr3-190387611-A-G is described in ClinVar as Benign. ClinVar VariationId is 1281821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378492.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN16	NM_001378492.1		c.-93-626A>G		intron	N/A	NP_001365421.1	Q9Y5I7
	CLDN16	NM_001378493.1		c.-93-626A>G		intron	N/A	NP_001365422.1	Q9Y5I7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN16	ENST00000880223.1		c.-93-626A>G		intron	N/A	ENSP00000550282.1
	CLDN16	ENST00000880225.1		c.-93-626A>G		intron	N/A	ENSP00000550284.1
	CLDN16	ENST00000880227.1		c.-93-626A>G		intron	N/A	ENSP00000550286.1

Frequencies

GnomAD3 genomes AF: 0.993 AC: 151103 AN: 152196 Hom.: 75010 Cov.: 31

Gnomad AFR AF: 0.998

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.995

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.995

Gnomad FIN AF: 0.999

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.989

Gnomad OTH AF: 0.989

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.993 AC: 151222 AN: 152314 Hom.: 75070 Cov.: 31 AF XY: 0.994 AC XY: 73988 AN XY: 74468

African (AFR) AF: 0.998 AC: 41474 AN: 41564

American (AMR) AF: 0.995 AC: 15230 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 3369 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5170 AN: 5170

South Asian (SAS) AF: 0.996 AC: 4803 AN: 4824

European-Finnish (FIN) AF: 0.999 AC: 10613 AN: 10626

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.989 AC: 67271 AN: 68040

Other (OTH) AF: 0.989 AC: 2088 AN: 2112

Alfa AF: 0.992 Hom.: 9341

Bravo AF: 0.993

Asia WGS AF: 0.999 AC: 3475 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.67
PhyloP100		-0.26

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9865730; hg19: chr3-190105400;