rs9644774

Variant names:

• chr8-8702322-G-A
• rs9644774
• ENST00000519106:c.-77G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-8702322-G-A
• chr8-8702322-G-C
• chr8-8702322-G-T

Variant summary

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

The NM_194284.3(CLDN23):​c.-77G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,425,858 control chromosomes in the GnomAD database, including 94,945 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 0.30 (7615 hom., cov: 34)
  • Exomes 𝑓: 0.36 (87330 hom.)
• Consequence: CLDN23 NM_194284.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470

Genes affected

CLDN23 (HGNC:17591): (claudin 23) 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, and also play critical roles in maintaining cell polarity and signal transductions. This gene is expressed in germinal center B-cells, placenta and stomach as well as in colon tumor. This gene is down-regulated in intestinal type gastric cancer. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN23	NM_194284.3	c.-77G>A		5_prime_UTR_variant	Exon 1 of 1	ENST00000519106.2	NP_919260.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN23	ENST00000519106	c.-77G>A		5_prime_UTR_variant	Exon 1 of 1		NM_194284.3	ENSP00000428780.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45752 AN: 152058 Hom.: 7619 Cov.: 34

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.0488

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.363 AC: 461869 AN: 1273682 Hom.: 87330 Cov.: 22 AF XY: 0.361 AC XY: 223894 AN XY: 620754

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.452

Gnomad4 EAS exome AF: 0.0687

Gnomad4 SAS exome AF: 0.255

Gnomad4 FIN exome AF: 0.312

Gnomad4 NFE exome AF: 0.388

Gnomad4 OTH exome AF: 0.343

GnomAD4 genome AF: 0.301 AC: 45760 AN: 152176 Hom.: 7615 Cov.: 34 AF XY: 0.293 AC XY: 21818 AN XY: 74392

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.0487

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.321

Alfa AF: 0.359 Hom.: 16472

Bravo AF: 0.290

Asia WGS AF: 0.148 AC: 513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.1
DANN	Benign	0.93

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: rs9644774; hg19: chr8-8559832; COSMIC: COSV67731496;