Variant 1-42733444-A-G 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 NM_148960.3(CLDN19):c.*1642T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,282 control chromosomes in the GnomAD database, including 3,009 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3006 hom., cov: 31)

Exomes 𝑓: 0.17 ( 3 hom. )

Consequence

CLDN19
NM_148960.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.01

Variant links:

Genes affected

CLDN19 (HGNC:2040): (claudin 19) The product of this gene belongs to the claudin family. It plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. Defects in this gene are the cause of hypomagnesemia renal with ocular involvement (HOMGO). HOMGO is a progressive renal disease characterized by primary renal magnesium wasting with hypomagnesemia, hypercalciuria and nephrocalcinosis associated with severe ocular abnormalities such as bilateral chorioretinal scars, macular colobomata, significant myopia and nystagmus. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jun 2010]

CLDN19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-42733444-A-G is Benign according to our data. Variant chr1-42733444-A-G is described in ClinVar as [Benign]. Clinvar id is 297318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
CLDN19	NM_148960.3 linkuse as main transcript	c.*1642T>C	3_prime_UTR_variant	5/5	ENST00000296387.6	NP_683763.2
CLDN19	NM_001123395.2 linkuse as main transcript	c.*2424T>C	3_prime_UTR_variant	4/4		NP_001116867.1
CLDN19	NM_001185117.2 linkuse as main transcript	c.*2318T>C	3_prime_UTR_variant	3/3		NP_001172046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN19	ENST00000296387.6 linkuse as main transcript	c.*1642T>C		3_prime_UTR_variant	5/5	2	NM_148960.3	ENSP00000296387		Q8N6F1-1
CLDN19	ENST00000539749.5 linkuse as main transcript	c.*2318T>C		3_prime_UTR_variant	3/3	2		ENSP00000443229		Q8N6F1-3

Frequencies

GnomAD3 genomes

AF:

0.189

AC:

28777

AN:

151982

Hom.:

3000

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.160

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.200

GnomAD4 exome

AF:

0.170

AC:

AN:

182

Hom.:

Cov.:

AF XY:

0.191

AC XY:

AN XY:

136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.250

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.333

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.100

Gnomad4 NFE exome

AF:

0.167

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.189

AC:

28805

AN:

152100

Hom.:

3006

Cov.:

AF XY:

0.185

AC XY:

13782

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.271

Gnomad4 AMR

AF:

0.170

Gnomad4 ASJ

AF:

0.244

Gnomad4 EAS

AF:

0.207

Gnomad4 SAS

AF:

0.125

Gnomad4 FIN

AF:

0.120

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.198

Alfa

AF:

0.176

Hom.:

505

Bravo

AF:

0.202

Asia WGS

AF:

0.172

AC:

595

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Renal hypomagnesemia 5 with ocular involvement

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.3

DANN

Benign

0.77

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