8-8702322-G-T

Variant names:

• chr8-8702322-G-T
• rs9644774
• NM_194284.3:c.-77G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_194284.3(CLDN23):​c.-77G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000784 in 1,274,968 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: 34)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: CLDN23 NM_194284.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 0 publications found

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]

ENSG00000254367 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN23	NM_194284.3	c.-77G>T		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	ENST00000519106.2	c.-77G>T		5_prime_UTR_variant	Exon 1 of 1	6	NM_194284.3	ENSP00000428780.1
ENSG00000254367	ENST00000765578.1	n.660+21208C>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.84e-7 AC: 1 AN: 1274968 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 621370

African (AFR) AF: 0.00 AC: 0 AN: 26242

American (AMR) AF: 0.00 AC: 0 AN: 21874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18240

East Asian (EAS) AF: 0.00 AC: 0 AN: 34632

South Asian (SAS) AF: 0.0000160 AC: 1 AN: 62582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33064

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3518

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1021684

Other (OTH) AF: 0.00 AC: 0 AN: 53132

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.9
DANN	Benign	0.87
PhyloP100		0.047
PromoterAI		-0.10	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9644774; hg19: chr8-8559832;