rs7637370

Variant names:

• chr3-138017627-C-T
• rs7637370
• NM_016369.4:c.221-6031C>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.221-6031C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,002 control chromosomes in the GnomAD database, including 11,889 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 0.38 (11889 hom., cov: 32)
• Consequence: CLDN18 NM_016369.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 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.221-6031C>T		intron	N/A	NP_057453.1
	CLDN18	NM_001002026.3		c.221-6031C>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.221-6031C>T		intron	N/A	ENSP00000183605.5
	CLDN18	ENST00000343735.8	TSL:1	c.221-6031C>T		intron	N/A	ENSP00000340939.4
	CLDN18	ENST00000479660.1	TSL:2	n.221-6031C>T		intron	N/A	ENSP00000419732.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57077 AN: 151886 Hom.: 11898 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.375 AC: 57070 AN: 152002 Hom.: 11889 Cov.: 32 AF XY: 0.368 AC XY: 27371 AN XY: 74302

African (AFR) AF: 0.202 AC: 8369 AN: 41448

American (AMR) AF: 0.354 AC: 5410 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1758 AN: 3472

East Asian (EAS) AF: 0.279 AC: 1441 AN: 5170

South Asian (SAS) AF: 0.411 AC: 1975 AN: 4804

European-Finnish (FIN) AF: 0.351 AC: 3706 AN: 10548

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32864 AN: 67966

Other (OTH) AF: 0.417 AC: 878 AN: 2108

Alfa AF: 0.451 Hom.: 50226

Bravo AF: 0.368

Asia WGS AF: 0.332 AC: 1158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.3
DANN	Benign	0.78
PhyloP100		0.61
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: rs7637370; hg19: chr3-137736469;