Variant 1-42733353-C-T 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.*1733G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,564 control chromosomes in the GnomAD database, including 1,175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1173 hom., cov: 32)

Exomes 𝑓: 0.091 ( 2 hom. )

Consequence

CLDN19
NM_148960.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.200

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=-0.95).

BP6

Variant 1-42733353-C-T is Benign according to our data. Variant chr1-42733353-C-T is described in ClinVar as [Benign]. Clinvar id is 297316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
CLDN19	NM_148960.3 linkuse as main transcript	c.*1733G>A	3_prime_UTR_variant	5/5	ENST00000296387.6	NP_683763.2
CLDN19	NM_001123395.2 linkuse as main transcript	c.*2515G>A	3_prime_UTR_variant	4/4		NP_001116867.1
CLDN19	NM_001185117.2 linkuse as main transcript	c.*2409G>A	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.*1733G>A		3_prime_UTR_variant	5/5	2	NM_148960.3	ENSP00000296387		Q8N6F1-1
CLDN19	ENST00000539749.5 linkuse as main transcript	c.*2409G>A		3_prime_UTR_variant	3/3	2		ENSP00000443229		Q8N6F1-3

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18520

AN:

152038

Hom.:

1173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.0684

Gnomad FIN

AF:

0.0901

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.130

GnomAD4 exome

AF:

0.0907

AC:

AN:

408

Hom.:

Cov.:

AF XY:

0.0987

AC XY:

AN XY:

314

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.0833

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0893

Gnomad4 OTH exome

AF:

0.0625

GnomAD4 genome

AF:

0.122

AC:

18532

AN:

152156

Hom.:

1173

Cov.:

AF XY:

0.119

AC XY:

8868

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.132

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.206

Gnomad4 SAS

AF:

0.0685

Gnomad4 FIN

AF:

0.0901

Gnomad4 NFE

AF:

0.115

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.125

Hom.:

142

Bravo

AF:

0.128

Asia WGS

AF:

0.142

AC:

491

AN:

3476

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

-0.95

CADD

Benign

1.8

DANN

Benign

0.25

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