18-65768024-C-T

Position:

• chr18-65768024-C-T

Variant summary

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

The NM_004361.5(CDH7):​c.210+4972C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,994 control chromosomes in the GnomAD database, including 17,695 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 (17695 hom., cov: 32)
• Consequence: CDH7 NM_004361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH7	NM_004361.5	c.210+4972C>T		intron_variant		ENST00000397968.4
CDH7	NM_001317214.3	c.210+4972C>T		intron_variant
CDH7	NM_001362438.2	c.210+4972C>T		intron_variant
CDH7	NM_033646.4	c.210+4972C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH7	ENST00000397968.4	c.210+4972C>T		intron_variant		1	NM_004361.5	P1
CDH7	ENST00000323011.7	c.210+4972C>T		intron_variant		1		P1
CDH7	ENST00000536984.6	c.210+4972C>T		intron_variant		1
CDH7	ENST00000581601.1	n.45+4972C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67098 AN: 151876 Hom.: 17646 Cov.: 32

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.481

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: 0.442 AC: 67192 AN: 151994 Hom.: 17695 Cov.: 32 AF XY: 0.445 AC XY: 33040 AN XY: 74290

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.386

Alfa AF: 0.331 Hom.: 8690

Bravo AF: 0.444

Asia WGS AF: 0.459 AC: 1596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.1
DANN	Benign	0.42

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: rs7237421; hg19: chr18-63435260;