rs10314

chr22-19523195-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363066.2(CLDN5):c.*404G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 194,704 control chromosomes in the GnomAD database, including 2,472 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 0.15 (1961 hom., cov: 33)
  • Exomes 𝑓: 0.14 (511 hom.)
• Consequence: CLDN5 NM_001363066.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

Genes affected

CLDN5 (HGNC:2047): (claudin 5) This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets. Mutations in this gene have been found in patients with velocardiofacial syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDN5	NM_001363066.2	c.*404G>C		3_prime_UTR_variant	1/1	ENST00000618236.2
CLDN5	NM_001130861.1	c.*404G>C		3_prime_UTR_variant	1/1
CLDN5	NM_001363067.2	c.*404G>C		3_prime_UTR_variant	2/2
CLDN5	NM_003277.4	c.*404G>C		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN5	ENST00000618236.2	c.*404G>C		3_prime_UTR_variant	1/1		NM_001363066.2	P1
CLDN5	ENST00000403084.1	c.*404G>C		3_prime_UTR_variant	1/1
CLDN5	ENST00000406028.1	c.*404G>C		3_prime_UTR_variant	2/2	2
CLDN5	ENST00000413119.2	c.*404G>C		3_prime_UTR_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23246 AN: 152006 Hom.: 1962 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.137 AC: 5822 AN: 42580 Hom.: 511 Cov.: 0 AF XY: 0.138 AC XY: 2884 AN XY: 20858

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.151

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.313

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.153 AC: 23249 AN: 152124 Hom.: 1961 Cov.: 33 AF XY: 0.154 AC XY: 11437 AN XY: 74346

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.140

Alfa AF: 0.149 Hom.: 229

Bravo AF: 0.158

Asia WGS AF: 0.198 AC: 687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	3.7
Dann	Benign	0.76

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: rs10314; hg19: chr22-19510718;