chr18-65822007-C-T

Position:

• chr18-65822007-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004361.5(CDH7):​c.626-74C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.055 in 1,169,118 control chromosomes in the GnomAD database, including 3,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (1221 hom., cov: 32)
  • Exomes 𝑓: 0.049 (2136 hom.)
• Consequence: CDH7 NM_004361.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.101

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 18-65822007-C-T is Benign according to our data. Variant chr18-65822007-C-T is described in ClinVar as [Benign]. Clinvar id is 1248353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH7	NM_004361.5	c.626-74C>T		intron_variant		ENST00000397968.4
CDH7	NM_001317214.3	c.626-74C>T		intron_variant
CDH7	NM_001362438.2	c.626-74C>T		intron_variant
CDH7	NM_033646.4	c.626-74C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH7	ENST00000397968.4	c.626-74C>T		intron_variant		1	NM_004361.5	P1
CDH7	ENST00000323011.7	c.626-74C>T		intron_variant		1		P1
CDH7	ENST00000536984.6	c.626-74C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0943 AC: 14343 AN: 152024 Hom.: 1218 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0949

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.0760

GnomAD4 exome AF: 0.0491 AC: 49917 AN: 1016976 Hom.: 2136 AF XY: 0.0509 AC XY: 26671 AN XY: 523880

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.0603

Gnomad4 ASJ exome AF: 0.0953

Gnomad4 EAS exome AF: 0.00963

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.0285

Gnomad4 NFE exome AF: 0.0358

Gnomad4 OTH exome AF: 0.0614

GnomAD4 genome AF: 0.0944 AC: 14355 AN: 152142 Hom.: 1221 Cov.: 32 AF XY: 0.0928 AC XY: 6907 AN XY: 74392

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.0621

Gnomad4 ASJ AF: 0.0949

Gnomad4 EAS AF: 0.0110

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.0318

Gnomad4 NFE AF: 0.0371

Gnomad4 OTH AF: 0.0762

Alfa AF: 0.0688 Hom.: 102

Bravo AF: 0.102

Asia WGS AF: 0.106 AC: 366 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.8
DANN	Benign	0.48

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: rs28722899; hg19: chr18-63489243;