17-7261244-C-T

Variant names:

• chr17-7261244-C-T
• rs222857
• NM_001307.6:c.224-259G>A

Variant summary

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

The NM_001307.6(CLDN7):​c.224-259G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 544,968 control chromosomes in the GnomAD database, including 86,471 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 0.52 (21230 hom., cov: 32)
  • Exomes 𝑓: 0.57 (65241 hom.)
• Consequence: CLDN7 NM_001307.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 38 publications found

Genes affected

CLDN7 (HGNC:2049): (claudin 7) 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. Differential expression of this gene has been observed in different types of malignancies, including breast cancer, ovarian cancer, hepatocellular carcinomas, urinary tumors, prostate cancer, lung cancer, head and neck cancers, thyroid carcinomas, etc.. Alternatively spliced transcript variants encoding different isoforms have been found.[provided by RefSeq, May 2010]

ENSG00000262302 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001307.6. 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
	CLDN7	NM_001307.6	MANE Select	c.224-259G>A		intron	N/A	NP_001298.3
	CLDN7	NM_001185022.2		c.224-259G>A		intron	N/A	NP_001171951.1	A0A384ME58
	CLDN7	NM_001185023.2		c.224-259G>A		intron	N/A	NP_001171952.1	F5H496

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN7	ENST00000360325.11	TSL:1 MANE Select	c.224-259G>A		intron	N/A	ENSP00000353475.7	O95471-1
	CLDN7	ENST00000397317.8	TSL:1	c.224-259G>A		intron	N/A	ENSP00000396638.3	O95471-1
	ENSG00000262302	ENST00000577138.1	TSL:3	n.223+577G>A		intron	N/A	ENSP00000460571.1	I3L3M4

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79114 AN: 151832 Hom.: 21206 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.550

GnomAD4 exome AF: 0.570 AC: 224004 AN: 393018 Hom.: 65241 AF XY: 0.575 AC XY: 119512 AN XY: 207844

African (AFR) AF: 0.395 AC: 3864 AN: 9772

American (AMR) AF: 0.510 AC: 7809 AN: 15316

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 6712 AN: 11690

East Asian (EAS) AF: 0.347 AC: 8763 AN: 25284

South Asian (SAS) AF: 0.620 AC: 26764 AN: 43160

European-Finnish (FIN) AF: 0.613 AC: 15520 AN: 25316

Middle Eastern (MID) AF: 0.661 AC: 1128 AN: 1706

European-Non Finnish (NFE) AF: 0.592 AC: 140927 AN: 238136

Other (OTH) AF: 0.553 AC: 12517 AN: 22638

GnomAD4 genome AF: 0.521 AC: 79185 AN: 151950 Hom.: 21230 Cov.: 32 AF XY: 0.525 AC XY: 39022 AN XY: 74280

African (AFR) AF: 0.389 AC: 16106 AN: 41450

American (AMR) AF: 0.531 AC: 8115 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1944 AN: 3466

East Asian (EAS) AF: 0.370 AC: 1896 AN: 5124

South Asian (SAS) AF: 0.609 AC: 2940 AN: 4826

European-Finnish (FIN) AF: 0.622 AC: 6586 AN: 10590

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39757 AN: 67908

Other (OTH) AF: 0.556 AC: 1175 AN: 2112

Alfa AF: 0.550 Hom.: 27210

Bravo AF: 0.503

Asia WGS AF: 0.499 AC: 1735 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.94
PhyloP100		0.19
PromoterAI		-0.039	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs222857; hg19: chr17-7164563;