3-138020088-G-T

Variant names:

• chr3-138020088-G-T
• rs3773770
• NM_016369.4:c.221-3570G>T

Variant summary

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

The NM_016369.4(CLDN18):​c.221-3570G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,952 control chromosomes in the GnomAD database, including 20,410 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 0.50 (20410 hom., cov: 32)
• Consequence: CLDN18 NM_016369.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 5 publications found

Genes affected

CLDN18 (HGNC:2039): (claudin 18) 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 upregulated in patients with ulcerative colitis and highly overexpressed in infiltrating ductal adenocarcinomas. PKC/MAPK/AP-1 (protein kinase C/mitogen-activated protein kinase/activator protein-1) dependent pathway regulates the expression of this gene in gastric cells. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jun 2010]

LOC105374127 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016369.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN18	NM_016369.4	MANE Select	c.221-3570G>T		intron	N/A	NP_057453.1
	CLDN18	NM_001002026.3		c.221-3570G>T		intron	N/A	NP_001002026.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN18	ENST00000183605.10	TSL:1 MANE Select	c.221-3570G>T		intron	N/A	ENSP00000183605.5
	CLDN18	ENST00000343735.8	TSL:1	c.221-3570G>T		intron	N/A	ENSP00000340939.4
	CLDN18	ENST00000479660.1	TSL:2	n.221-3570G>T		intron	N/A	ENSP00000419732.1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76150 AN: 151834 Hom.: 20414 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.518

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.501 AC: 76178 AN: 151952 Hom.: 20410 Cov.: 32 AF XY: 0.498 AC XY: 37023 AN XY: 74270

African (AFR) AF: 0.330 AC: 13689 AN: 41420

American (AMR) AF: 0.452 AC: 6913 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2273 AN: 3472

East Asian (EAS) AF: 0.309 AC: 1593 AN: 5152

South Asian (SAS) AF: 0.524 AC: 2516 AN: 4804

European-Finnish (FIN) AF: 0.571 AC: 6027 AN: 10564

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41188 AN: 67940

Other (OTH) AF: 0.517 AC: 1093 AN: 2114

Alfa AF: 0.577 Hom.: 13845

Bravo AF: 0.481

Asia WGS AF: 0.398 AC: 1385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.0
DANN	Benign	0.75
PhyloP100		0.18
Mutation Taster		=100/0	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: rs3773770; hg19: chr3-137738930;