dbSNP rs10314: CLDN5:c.*404G>C (chr22-19523195-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.02

Publications

18 publications found

Variant links:

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]

CLDN5 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: G2P

CLDN5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
CLDN5	NM_001363066.2 link	c.*404G>C	3_prime_UTR_variant	Exon 1 of 1	ENST00000618236.2	NP_001349995.1
CLDN5	NM_001130861.1 link	c.*404G>C	3_prime_UTR_variant	Exon 1 of 1		NP_001124333.1	O00501D3DX19
CLDN5	NM_001363067.2 link	c.*404G>C	3_prime_UTR_variant	Exon 2 of 2		NP_001349996.1
CLDN5	NM_003277.4 link	c.*404G>C	3_prime_UTR_variant	Exon 2 of 2		NP_003268.2	O00501D3DX19

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CLDN5	ENST00000618236.2 link	c.*404G>C	3_prime_UTR_variant	Exon 1 of 1	6	NM_001363066.2	ENSP00000480623.1	O00501
CLDN5	ENST00000403084.1 link	c.*404G>C	3_prime_UTR_variant	Exon 1 of 1	6		ENSP00000384554.1	D3DX19
CLDN5	ENST00000406028.1 link	c.*404G>C	3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000385477.1	D3DX19
CLDN5	ENST00000413119.2 link	c.*404G>C	3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000400612.2	D3DX19

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23246

AN:

152006

Hom.:

1962

Cov.:

show subpopulations

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.:

AF XY:

0.138

AC XY:

2884

AN XY:

20858

show subpopulations

African (AFR)

AF:

0.180

AC:

168

AN:

934

American (AMR)

AF:

0.151

AC:

187

AN:

1238

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

138

AN:

1292

East Asian (EAS)

AF:

0.313

AC:

442

AN:

1412

South Asian (SAS)

AF:

0.133

AC:

330

AN:

2482

European-Finnish (FIN)

AF:

0.129

AC:

284

AN:

2196

Middle Eastern (MID)

AF:

0.136

AC:

AN:

184

European-Non Finnish (NFE)

AF:

0.129

AC:

3892

AN:

30104

Other (OTH)

AF:

0.130

AC:

356

AN:

2738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

235

471

706

942

1177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.153

AC:

23249

AN:

152124

Hom.:

1961

Cov.:

AF XY:

0.154

AC XY:

11437

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.176

AC:

7325

AN:

41502

American (AMR)

AF:

0.141

AC:

2158

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

373

AN:

3472

East Asian (EAS)

AF:

0.312

AC:

1608

AN:

5160

South Asian (SAS)

AF:

0.136

AC:

655

AN:

4824

European-Finnish (FIN)

AF:

0.144

AC:

1525

AN:

10584

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9083

AN:

67982

Other (OTH)

AF:

0.140

AC:

296

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1010

2019

3029

4038

5048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.76

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over