NM_004361.5:c.489C>G

Variant names:

• chr18-65809982-C-G
• rs7235166
• NM_004361.5:c.489C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004361.5(CDH7):​c.489C>G​(p.Pro163Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00479 in 1,609,634 control chromosomes in the GnomAD database, including 325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (158 hom., cov: 31)
  • Exomes 𝑓: 0.0026 (167 hom.)
• Consequence: CDH7 NM_004361.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -6.71
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 18-65809982-C-G is Benign according to our data. Variant chr18-65809982-C-G is described in ClinVar as [Benign]. Clinvar id is 768939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.71 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH7	NM_004361.5	c.489C>G	p.Pro163Pro	synonymous_variant	Exon 3 of 12	ENST00000397968.4	NP_004352.2
CDH7	NM_001362438.2	c.489C>G	p.Pro163Pro	synonymous_variant	Exon 3 of 12		NP_001349367.1
CDH7	NM_033646.4	c.489C>G	p.Pro163Pro	synonymous_variant	Exon 3 of 12		NP_387450.1
CDH7	NM_001317214.3	c.489C>G	p.Pro163Pro	synonymous_variant	Exon 3 of 11		NP_001304143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH7	ENST00000397968.4	c.489C>G	p.Pro163Pro	synonymous_variant	Exon 3 of 12	1	NM_004361.5	ENSP00000381058.2
CDH7	ENST00000323011.7	c.489C>G	p.Pro163Pro	synonymous_variant	Exon 3 of 12	1		ENSP00000319166.3
CDH7	ENST00000536984.6	c.489C>G	p.Pro163Pro	synonymous_variant	Exon 3 of 11	1		ENSP00000443030.2

Frequencies

GnomAD3 genomes AF: 0.0254 AC: 3851 AN: 151704 Hom.: 158 Cov.: 31

Gnomad AFR AF: 0.0892

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00834

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00695 AC: 1736 AN: 249638 AF XY: 0.00519

Gnomad AFR exome AF: 0.0924

Gnomad AMR exome AF: 0.00535

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000187

Gnomad OTH exome AF: 0.00443

GnomAD4 exome AF: 0.00264 AC: 3844 AN: 1457812 Hom.: 167 Cov.: 32 AF XY: 0.00227 AC XY: 1647 AN XY: 724310

African (AFR) AF: 0.0932 AC: 3115 AN: 33408

American (AMR) AF: 0.00575 AC: 257 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39584

South Asian (SAS) AF: 0.000244 AC: 21 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5746

European-Non Finnish (NFE) AF: 0.0000668 AC: 74 AN: 1108496

Other (OTH) AF: 0.00600 AC: 361 AN: 60204

GnomAD4 genome AF: 0.0254 AC: 3862 AN: 151822 Hom.: 158 Cov.: 31 AF XY: 0.0239 AC XY: 1771 AN XY: 74198

African (AFR) AF: 0.0892 AC: 3690 AN: 41366

American (AMR) AF: 0.00833 AC: 127 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67966

Other (OTH) AF: 0.0128 AC: 27 AN: 2110

Alfa AF: 0.00120 Hom.: 2

Bravo AF: 0.0294

Asia WGS AF: 0.00520 AC: 19 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.011
DANN	Benign	0.24
PhyloP100		-6.7
Mutation Taster		=98/2	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: rs7235166; hg19: chr18-63477218;