3-138017627-C-T

Position:

• chr3-138017627-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN18	NM_016369.4	c.221-6031C>T		intron_variant		ENST00000183605.10	NP_057453.1
LOC105374127	XR_007096112.1	n.2710G>A		non_coding_transcript_exon_variant	3/3
CLDN18	NM_001002026.3	c.221-6031C>T		intron_variant			NP_001002026.1
LOC105374127	XR_924534.3	n.3740G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN18	ENST00000183605.10	c.221-6031C>T		intron_variant		1	NM_016369.4	ENSP00000183605	P4
CLDN18	ENST00000343735.8	c.221-6031C>T		intron_variant		1		ENSP00000340939	A1
CLDN18	ENST00000479660.1	c.221-6031C>T		intron_variant, NMD_transcript_variant		2		ENSP00000419732

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

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.417

Alfa AF: 0.474 Hom.: 35176

Bravo AF: 0.368

Asia WGS AF: 0.332 AC: 1158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.3
DANN	Benign	0.78

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: rs7637370; hg19: chr3-137736469;