chr18-65809970-G-A

Variant names:

• chr18-65809970-G-A
• rs17075229
• NM_004361.5:c.477G>A

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.477G>A​(p.Thr159Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.02 in 1,611,472 control chromosomes in the GnomAD database, including 678 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (88 hom., cov: 31)
  • Exomes 𝑓: 0.020 (590 hom.)
• Consequence: CDH7 NM_004361.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.62
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 18-65809970-G-A is Benign according to our data. Variant chr18-65809970-G-A is described in ClinVar as [Benign]. Clinvar id is 1244452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.62 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH7	NM_004361.5	c.477G>A	p.Thr159Thr	synonymous_variant	Exon 3 of 12	ENST00000397968.4	NP_004352.2
CDH7	NM_001362438.2	c.477G>A	p.Thr159Thr	synonymous_variant	Exon 3 of 12		NP_001349367.1
CDH7	NM_033646.4	c.477G>A	p.Thr159Thr	synonymous_variant	Exon 3 of 12		NP_387450.1
CDH7	NM_001317214.3	c.477G>A	p.Thr159Thr	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.477G>A	p.Thr159Thr	synonymous_variant	Exon 3 of 12	1	NM_004361.5	ENSP00000381058.2
CDH7	ENST00000323011.7	c.477G>A	p.Thr159Thr	synonymous_variant	Exon 3 of 12	1		ENSP00000319166.3
CDH7	ENST00000536984.6	c.477G>A	p.Thr159Thr	synonymous_variant	Exon 3 of 11	1		ENSP00000443030.2

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3104 AN: 151952 Hom.: 88 Cov.: 31

Gnomad AFR AF: 0.00452

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0726

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.000968

Gnomad SAS AF: 0.00954

Gnomad FIN AF: 0.0294

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0200

Gnomad OTH AF: 0.0211

GnomAD2 exomes AF: 0.0302 AC: 7566 AN: 250168 AF XY: 0.0265

Gnomad AFR exome AF: 0.00389

Gnomad AMR exome AF: 0.121

Gnomad ASJ exome AF: 0.00755

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0352

Gnomad NFE exome AF: 0.0181

Gnomad OTH exome AF: 0.0250

GnomAD4 exome AF: 0.0200 AC: 29127 AN: 1459402 Hom.: 590 Cov.: 32 AF XY: 0.0195 AC XY: 14153 AN XY: 725486

African (AFR) AF: 0.00311 AC: 104 AN: 33440

American (AMR) AF: 0.115 AC: 5125 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00873 AC: 228 AN: 26118

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39628

South Asian (SAS) AF: 0.0108 AC: 930 AN: 86224

European-Finnish (FIN) AF: 0.0318 AC: 1701 AN: 53410

Middle Eastern (MID) AF: 0.00382 AC: 22 AN: 5752

European-Non Finnish (NFE) AF: 0.0181 AC: 20047 AN: 1109858

Other (OTH) AF: 0.0160 AC: 967 AN: 60286

GnomAD4 genome AF: 0.0204 AC: 3109 AN: 152070 Hom.: 88 Cov.: 31 AF XY: 0.0218 AC XY: 1624 AN XY: 74330

African (AFR) AF: 0.00451 AC: 187 AN: 41494

American (AMR) AF: 0.0728 AC: 1112 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3472

East Asian (EAS) AF: 0.000970 AC: 5 AN: 5152

South Asian (SAS) AF: 0.00976 AC: 47 AN: 4818

European-Finnish (FIN) AF: 0.0294 AC: 311 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0200 AC: 1362 AN: 67992

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.0186 Hom.: 23

Bravo AF: 0.0232

Asia WGS AF: 0.0120 AC: 41 AN: 3478

EpiCase AF: 0.0171

EpiControl AF: 0.0143

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.78
CADD	Benign	0.089
DANN	Benign	0.81
PhyloP100		-2.6
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: rs17075229; hg19: chr18-63477206; COSMIC: COSV107386632;