chr18-65777480-G-A

Position:

• chr18-65777480-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004361.5(CDH7):​c.210+14428G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,464 control chromosomes in the GnomAD database, including 10,208 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 0.36 (10208 hom., cov: 30)
• Consequence: CDH7 NM_004361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH7	NM_004361.5	c.210+14428G>A		intron_variant		ENST00000397968.4
CDH7	NM_001317214.3	c.210+14428G>A		intron_variant
CDH7	NM_001362438.2	c.210+14428G>A		intron_variant
CDH7	NM_033646.4	c.210+14428G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH7	ENST00000397968.4	c.210+14428G>A		intron_variant		1	NM_004361.5	P1
CDH7	ENST00000323011.7	c.210+14428G>A		intron_variant		1		P1
CDH7	ENST00000536984.6	c.210+14428G>A		intron_variant		1
CDH7	ENST00000581601.1	n.45+14428G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54102 AN: 151346 Hom.: 10178 Cov.: 30

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.358 AC: 54173 AN: 151464 Hom.: 10208 Cov.: 30 AF XY: 0.364 AC XY: 26919 AN XY: 73992

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.316

Alfa AF: 0.311 Hom.: 12654

Bravo AF: 0.347

Asia WGS AF: 0.417 AC: 1448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.9
DANN	Benign	0.55

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: rs1484725; hg19: chr18-63444716;