chr3-190307888-C-A

Variant names:

• chr3-190307888-C-A
• rs55724972
• NM_021101.5:c.*389G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021101.5(CLDN1):​c.*389G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0584 in 164,672 control chromosomes in the GnomAD database, including 361 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.058 (331 hom., cov: 32)
  • Exomes 𝑓: 0.063 (30 hom.)
• Consequence: CLDN1 NM_021101.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420
• Publications: 4 publications found

Genes affected

CLDN1 (HGNC:2032): (claudin 1) 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. Loss of function mutations result in neonatal ichthyosis-sclerosing cholangitis syndrome. [provided by RefSeq, Jul 2008]

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]

P3H2-AS1 (HGNC:40886): (P3H2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0802 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021101.5. 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
	CLDN1	NM_021101.5	MANE Select	c.*389G>T		3_prime_UTR	Exon 4 of 4	NP_066924.1	O95832
	CLDN16	NM_001378492.1		c.-445-7005C>A		intron	N/A	NP_001365421.1	Q9Y5I7
	CLDN16	NM_001378493.1		c.-279+17297C>A		intron	N/A	NP_001365422.1	Q9Y5I7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN1	ENST00000295522.4	TSL:1 MANE Select	c.*389G>T		3_prime_UTR	Exon 4 of 4	ENSP00000295522.3	O95832
	P3H2-AS1	ENST00000747181.1		n.627-7005C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8811 AN: 151884 Hom.: 331 Cov.: 32

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.0651

Gnomad ASJ AF: 0.0880

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.0565

Gnomad FIN AF: 0.0698

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0820

Gnomad OTH AF: 0.0854

GnomAD4 exome AF: 0.0632 AC: 801 AN: 12670 Hom.: 30 Cov.: 0 AF XY: 0.0640 AC XY: 452 AN XY: 7060

African (AFR) AF: 0.00893 AC: 1 AN: 112

American (AMR) AF: 0.0652 AC: 117 AN: 1794

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 17 AN: 170

East Asian (EAS) AF: 0.00159 AC: 1 AN: 628

South Asian (SAS) AF: 0.0497 AC: 90 AN: 1810

European-Finnish (FIN) AF: 0.0538 AC: 14 AN: 260

Middle Eastern (MID) AF: 0.0556 AC: 2 AN: 36

European-Non Finnish (NFE) AF: 0.0714 AC: 526 AN: 7370

Other (OTH) AF: 0.0673 AC: 33 AN: 490

GnomAD4 genome AF: 0.0580 AC: 8812 AN: 152002 Hom.: 331 Cov.: 32 AF XY: 0.0569 AC XY: 4224 AN XY: 74290

African (AFR) AF: 0.0150 AC: 621 AN: 41488

American (AMR) AF: 0.0650 AC: 991 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0880 AC: 305 AN: 3466

East Asian (EAS) AF: 0.00406 AC: 21 AN: 5170

South Asian (SAS) AF: 0.0567 AC: 273 AN: 4812

European-Finnish (FIN) AF: 0.0698 AC: 736 AN: 10546

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0820 AC: 5576 AN: 67962

Other (OTH) AF: 0.0850 AC: 179 AN: 2106

Alfa AF: 0.0740 Hom.: 164

Bravo AF: 0.0560

Asia WGS AF: 0.0250 AC: 91 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.58
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs55724972; hg19: chr3-190025677;