chr3-190308016-G-T

Position:

• chr3-190308016-G-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.*261C>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 0.622 in 406,692 control chromosomes in the GnomAD database, including 81,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (34385 hom., cov: 30)
  • Exomes 𝑓: 0.60 (46633 hom.)
• Consequence: CLDN1 NM_021101.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.239

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=-0.9).
• BP6: Variant 3-190308016-G-T is Benign according to our data. Variant chr3-190308016-G-T is described in ClinVar as [Benign]. Clinvar id is 1266027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDN1	NM_021101.5	c.*261C>A		3_prime_UTR_variant	4/4	ENST00000295522.4
CLDN16	NM_001378492.1	c.-445-6877G>T		intron_variant
CLDN16	NM_001378493.1	c.-279+17425G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN1	ENST00000295522.4	c.*261C>A		3_prime_UTR_variant	4/4	1	NM_021101.5	P1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100484 AN: 151680 Hom.: 34341 Cov.: 30

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.649

GnomAD4 exome AF: 0.598 AC: 152331 AN: 254894 Hom.: 46633 Cov.: 3 AF XY: 0.594 AC XY: 81521 AN XY: 137160

Gnomad4 AFR exome AF: 0.834

Gnomad4 AMR exome AF: 0.610

Gnomad4 ASJ exome AF: 0.508

Gnomad4 EAS exome AF: 0.822

Gnomad4 SAS exome AF: 0.547

Gnomad4 FIN exome AF: 0.572

Gnomad4 NFE exome AF: 0.582

Gnomad4 OTH exome AF: 0.595

GnomAD4 genome AF: 0.663 AC: 100574 AN: 151798 Hom.: 34385 Cov.: 30 AF XY: 0.661 AC XY: 48972 AN XY: 74142

Gnomad4 AFR AF: 0.831

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.646

Alfa AF: 0.628 Hom.: 6550

Bravo AF: 0.675

Asia WGS AF: 0.620 AC: 2151 AN: 3472

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	-0.90
CADD	Benign	1.7
DANN	Benign	0.21

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: rs1043747; hg19: chr3-190025805;