chr8-8702388-G-A

Variant names:

• chr8-8702388-G-A
• rs11995449
• NM_194284.3:c.-11G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194284.3(CLDN23):​c.-11G>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 0.259 in 1,473,330 control chromosomes in the GnomAD database, including 51,707 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 0.24 (4975 hom., cov: 33)
  • Exomes 𝑓: 0.26 (46732 hom.)
• Consequence: CLDN23 NM_194284.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463
• Publications: 14 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194284.3. 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
	CLDN23	NM_194284.3	MANE Select	c.-11G>A		5_prime_UTR	Exon 1 of 1	NP_919260.2	Q96B33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN23	ENST00000519106.2	TSL:6 MANE Select	c.-11G>A		5_prime_UTR	Exon 1 of 1	ENSP00000428780.1	Q96B33
	ENSG00000254367	ENST00000765578.1		n.660+21142C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36893 AN: 152058 Hom.: 4961 Cov.: 33

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.223

GnomAD2 exomes AF: 0.308 AC: 38852 AN: 126026 AF XY: 0.306

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.402

Gnomad ASJ exome AF: 0.219

Gnomad EAS exome AF: 0.443

Gnomad FIN exome AF: 0.350

Gnomad NFE exome AF: 0.259

Gnomad OTH exome AF: 0.309

GnomAD4 exome AF: 0.261 AC: 344297 AN: 1321154 Hom.: 46732 Cov.: 33 AF XY: 0.264 AC XY: 170641 AN XY: 646484

African (AFR) AF: 0.146 AC: 3868 AN: 26506

American (AMR) AF: 0.372 AC: 9879 AN: 26544

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 3786 AN: 18858

East Asian (EAS) AF: 0.410 AC: 14050 AN: 34228

South Asian (SAS) AF: 0.389 AC: 25741 AN: 66214

European-Finnish (FIN) AF: 0.335 AC: 14338 AN: 42788

Middle Eastern (MID) AF: 0.236 AC: 859 AN: 3636

European-Non Finnish (NFE) AF: 0.246 AC: 257372 AN: 1048210

Other (OTH) AF: 0.266 AC: 14404 AN: 54170

GnomAD4 genome AF: 0.243 AC: 36945 AN: 152176 Hom.: 4975 Cov.: 33 AF XY: 0.251 AC XY: 18650 AN XY: 74412

African (AFR) AF: 0.156 AC: 6464 AN: 41544

American (AMR) AF: 0.296 AC: 4527 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 709 AN: 3466

East Asian (EAS) AF: 0.443 AC: 2276 AN: 5132

South Asian (SAS) AF: 0.395 AC: 1906 AN: 4822

European-Finnish (FIN) AF: 0.345 AC: 3657 AN: 10610

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16578 AN: 67974

Other (OTH) AF: 0.231 AC: 489 AN: 2116

Alfa AF: 0.164 Hom.: 415

Bravo AF: 0.235

Asia WGS AF: 0.436 AC: 1514 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.97
PhyloP100		-0.46
PromoterAI		-0.016	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11995449; hg19: chr8-8559898;