18-65771905-T-G

Variant names:

• chr18-65771905-T-G
• rs8092259
• NM_004361.5:c.210+8853T>G

Variant summary

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

The NM_004361.5(CDH7):​c.210+8853T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 151,852 control chromosomes in the GnomAD database, including 17,500 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 0.44 (17500 hom., cov: 31)
• Consequence: CDH7 NM_004361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 3 publications found

Genes affected

CDH7 (HGNC:1766): (cadherin 7) This gene encodes a type II classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium dependent cell-cell adhesion molecule is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Type II (atypical) cadherins are defined based on their lack of a histidine-alanine-valine (HAV) cell adhesion recognition sequence specific to type I cadherins. Cadherins mediate cell-cell binding in a homophilic manner, contributing to the sorting of heterogeneous cell types. Mutations in this gene may be associated with bipolar disease in human patients. This gene is present in a gene cluster on chromosome 18. [provided by RefSeq, May 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH7	NM_004361.5	c.210+8853T>G		intron_variant	Intron 2 of 11	ENST00000397968.4	NP_004352.2
CDH7	NM_001362438.2	c.210+8853T>G		intron_variant	Intron 2 of 11		NP_001349367.1
CDH7	NM_033646.4	c.210+8853T>G		intron_variant	Intron 2 of 11		NP_387450.1
CDH7	NM_001317214.3	c.210+8853T>G		intron_variant	Intron 2 of 10		NP_001304143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH7	ENST00000397968.4	c.210+8853T>G		intron_variant	Intron 2 of 11	1	NM_004361.5	ENSP00000381058.2
CDH7	ENST00000323011.7	c.210+8853T>G		intron_variant	Intron 2 of 11	1		ENSP00000319166.3
CDH7	ENST00000536984.6	c.210+8853T>G		intron_variant	Intron 2 of 10	1		ENSP00000443030.2
CDH7	ENST00000581601.1	n.45+8853T>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66799 AN: 151734 Hom.: 17452 Cov.: 31

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.441 AC: 66893 AN: 151852 Hom.: 17500 Cov.: 31 AF XY: 0.443 AC XY: 32912 AN XY: 74228

African (AFR) AF: 0.739 AC: 30608 AN: 41422

American (AMR) AF: 0.319 AC: 4867 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 967 AN: 3470

East Asian (EAS) AF: 0.346 AC: 1782 AN: 5146

South Asian (SAS) AF: 0.443 AC: 2128 AN: 4808

European-Finnish (FIN) AF: 0.411 AC: 4330 AN: 10528

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20878 AN: 67922

Other (OTH) AF: 0.387 AC: 815 AN: 2106

Alfa AF: 0.433 Hom.: 3038

Bravo AF: 0.442

Asia WGS AF: 0.461 AC: 1602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.7
DANN	Benign	0.57
PhyloP100		0.012
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: rs8092259; hg19: chr18-63439141;