chr18-65809757-C-T

Variant names:

• chr18-65809757-C-T
• rs61741837
• NM_004361.5:c.264C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_004361.5(CDH7):​c.264C>T​(p.Gly88Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,613,854 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (73 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (77 hom.)
• Consequence: CDH7 NM_004361.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.47
• Publications: 0 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 18-65809757-C-T is Benign according to our data. Variant chr18-65809757-C-T is described in ClinVar as [Benign]. Clinvar id is 775401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH7	NM_004361.5	c.264C>T	p.Gly88Gly	synonymous_variant	Exon 3 of 12	ENST00000397968.4	NP_004352.2
CDH7	NM_001362438.2	c.264C>T	p.Gly88Gly	synonymous_variant	Exon 3 of 12		NP_001349367.1
CDH7	NM_033646.4	c.264C>T	p.Gly88Gly	synonymous_variant	Exon 3 of 12		NP_387450.1
CDH7	NM_001317214.3	c.264C>T	p.Gly88Gly	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.264C>T	p.Gly88Gly	synonymous_variant	Exon 3 of 12	1	NM_004361.5	ENSP00000381058.2
CDH7	ENST00000323011.7	c.264C>T	p.Gly88Gly	synonymous_variant	Exon 3 of 12	1		ENSP00000319166.3
CDH7	ENST00000536984.6	c.264C>T	p.Gly88Gly	synonymous_variant	Exon 3 of 11	1		ENSP00000443030.2

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2724 AN: 152014 Hom.: 73 Cov.: 32

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00845

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00461 AC: 1158 AN: 251306 AF XY: 0.00331

Gnomad AFR exome AF: 0.0616

Gnomad AMR exome AF: 0.00275

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000264

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00186 AC: 2713 AN: 1461722 Hom.: 77 Cov.: 32 AF XY: 0.00156 AC XY: 1133 AN XY: 727162

African (AFR) AF: 0.0625 AC: 2092 AN: 33468

American (AMR) AF: 0.00322 AC: 144 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00486 AC: 28 AN: 5760

European-Non Finnish (NFE) AF: 0.000160 AC: 178 AN: 1111878

Other (OTH) AF: 0.00414 AC: 250 AN: 60392

GnomAD4 genome AF: 0.0179 AC: 2723 AN: 152132 Hom.: 73 Cov.: 32 AF XY: 0.0176 AC XY: 1311 AN XY: 74358

African (AFR) AF: 0.0614 AC: 2547 AN: 41482

American (AMR) AF: 0.00844 AC: 129 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68006

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.00349 Hom.: 8

Bravo AF: 0.0202

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 27, 2018

Labcorp Genetics (formerly Invitae), Labcorp

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	-0.38
CADD	Benign	14
DANN	Benign	0.58
PhyloP100		-1.5
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs61741837; hg19: chr18-63476993; COSMIC: COSV105900353;