rs1178386071

Variant names:

• chr1-42733178-G-A
• rs1178386071
• NM_148960.3:c.*1908C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-42733178-G-A
• chr1-42733178-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_148960.3(CLDN19):​c.*1908C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLDN19 NM_148960.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.724
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• renal hypomagnesemia 5 with ocular involvement

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148960.3. 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
	CLDN19	NM_148960.3	MANE Select	c.*1908C>T		3_prime_UTR	Exon 5 of 5	NP_683763.2	Q8N6F1-1
	CLDN19	NM_001185117.2		c.*2584C>T		3_prime_UTR	Exon 3 of 3	NP_001172046.1	Q8N6F1-3
	CLDN19	NM_001123395.2		c.*2690C>T		3_prime_UTR	Exon 4 of 4	NP_001116867.1	Q8N6F1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN19	ENST00000296387.6	TSL:2 MANE Select	c.*1908C>T		3_prime_UTR	Exon 5 of 5	ENSP00000296387.1	Q8N6F1-1
	CLDN19	ENST00000539749.5	TSL:2	c.*2584C>T		3_prime_UTR	Exon 3 of 3	ENSP00000443229.1	Q8N6F1-3

Frequencies

GnomAD3 genomes AF: 0.000242 AC: 31 AN: 128130 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000209

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000794

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000719

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00148

Gnomad MID AF: 0.0120

Gnomad NFE AF: 0.0000989

Gnomad OTH AF: 0.000577

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 256 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 194

African (AFR) AF: 0.00 AC: 0 AN: 10

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 6

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 204

Other (OTH) AF: 0.00 AC: 0 AN: 16

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000234 AC: 30 AN: 128188 Hom.: 0 Cov.: 30 AF XY: 0.000273 AC XY: 17 AN XY: 62236

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000208 AC: 7 AN: 33574

American (AMR) AF: 0.0000793 AC: 1 AN: 12614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3148

East Asian (EAS) AF: 0.000721 AC: 3 AN: 4162

South Asian (SAS) AF: 0.00 AC: 0 AN: 3924

European-Finnish (FIN) AF: 0.00148 AC: 11 AN: 7448

Middle Eastern (MID) AF: 0.00649 AC: 1 AN: 154

European-Non Finnish (NFE) AF: 0.0000989 AC: 6 AN: 60644

Other (OTH) AF: 0.000573 AC: 1 AN: 1746

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000169 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Renal hypomagnesemia 5 with ocular involvement (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.49
PhyloP100		0.72

Splicing

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

Other links and lift over

dbSNP: rs1178386071; hg19: chr1-43198849;