3-190308594-C-T

Position:

• chr3-190308594-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021101.5(CLDN1):​c.474-155G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,046 control chromosomes in the GnomAD database, including 35,661 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.67 (35661 hom., cov: 32)
• Consequence: CLDN1 NM_021101.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.10

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:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-190308594-C-T is Benign according to our data. Variant chr3-190308594-C-T is described in ClinVar as [Benign]. Clinvar id is 1250876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDN1	NM_021101.5	c.474-155G>A		intron_variant		ENST00000295522.4
CLDN16	NM_001378492.1	c.-445-6299C>T		intron_variant
CLDN16	NM_001378493.1	c.-279+18003C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN1	ENST00000295522.4	c.474-155G>A		intron_variant		1	NM_021101.5	P1

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102087 AN: 151928 Hom.: 35606 Cov.: 32

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.672 AC: 102192 AN: 152046 Hom.: 35661 Cov.: 32 AF XY: 0.670 AC XY: 49776 AN XY: 74306

Gnomad4 AFR AF: 0.865

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.653

Alfa AF: 0.583 Hom.: 4135

Bravo AF: 0.686

Asia WGS AF: 0.626 AC: 2176 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs12629166; hg19: chr3-190026383;