rs10503102

Variant names:

• chr18-65784734-G-A
• rs10503102
• NM_004361.5:c.210+21682G>A

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+21682G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,922 control chromosomes in the GnomAD database, including 8,865 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 0.34 (8865 hom., cov: 32)
• Consequence: CDH7 NM_004361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 1 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=-1.06).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004361.5. 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
	CDH7	NM_004361.5	MANE Select	c.210+21682G>A		intron	N/A	NP_004352.2
	CDH7	NM_001362438.2		c.210+21682G>A		intron	N/A	NP_001349367.1	Q9ULB5
	CDH7	NM_033646.4		c.210+21682G>A		intron	N/A	NP_387450.1	Q9ULB5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH7	ENST00000397968.4	TSL:1 MANE Select	c.210+21682G>A		intron	N/A	ENSP00000381058.2	Q9ULB5
	CDH7	ENST00000323011.7	TSL:1	c.210+21682G>A		intron	N/A	ENSP00000319166.3	Q9ULB5
	CDH7	ENST00000536984.6	TSL:1	c.210+21682G>A		intron	N/A	ENSP00000443030.2	F5H5X9

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51047 AN: 151804 Hom.: 8848 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.336 AC: 51088 AN: 151922 Hom.: 8865 Cov.: 32 AF XY: 0.343 AC XY: 25422 AN XY: 74212

African (AFR) AF: 0.386 AC: 15998 AN: 41428

American (AMR) AF: 0.277 AC: 4229 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3466

East Asian (EAS) AF: 0.305 AC: 1568 AN: 5136

South Asian (SAS) AF: 0.436 AC: 2100 AN: 4818

European-Finnish (FIN) AF: 0.412 AC: 4339 AN: 10536

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20756 AN: 67948

Other (OTH) AF: 0.302 AC: 637 AN: 2110

Alfa AF: 0.328 Hom.: 1061

Bravo AF: 0.322

Asia WGS AF: 0.408 AC: 1418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.17
DANN	Benign	0.74
PhyloP100		-1.7
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: rs10503102; hg19: chr18-63451970;