chr22-19523788-C-T

Variant names:

• chr22-19523788-C-T
• rs1479084723
• NM_001363066.2:c.468G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001363066.2(CLDN5):​c.468G>A​(p.Gln156Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,012 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CLDN5 NM_001363066.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=2.17 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363066.2. 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
	CLDN5	NM_001363066.2	MANE Select	c.468G>A	p.Gln156Gln	synonymous	Exon 1 of 1	NP_001349995.1	O00501
	CLDN5	NM_001130861.1		c.723G>A	p.Gln241Gln	synonymous	Exon 1 of 1	NP_001124333.1	O00501
	CLDN5	NM_001363067.2		c.723G>A	p.Gln241Gln	synonymous	Exon 2 of 2	NP_001349996.1	D3DX19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN5	ENST00000618236.2	TSL:6 MANE Select	c.468G>A	p.Gln156Gln	synonymous	Exon 1 of 1	ENSP00000480623.1	O00501
	CLDN5	ENST00000403084.1	TSL:6	c.723G>A	p.Gln241Gln	synonymous	Exon 1 of 1	ENSP00000384554.1	D3DX19
	CLDN5	ENST00000406028.1	TSL:2	c.723G>A	p.Gln241Gln	synonymous	Exon 2 of 2	ENSP00000385477.1	D3DX19

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454012 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722814

African (AFR) AF: 0.00 AC: 0 AN: 33362

American (AMR) AF: 0.00 AC: 0 AN: 43550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25960

East Asian (EAS) AF: 0.00 AC: 0 AN: 39396

South Asian (SAS) AF: 0.00 AC: 0 AN: 85474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109056

Other (OTH) AF: 0.00 AC: 0 AN: 60062

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Uncertain	0.98
PhyloP100		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1479084723; hg19: chr22-19511311;