18-65762893-T-A

Variant names:

• chr18-65762893-T-A
• rs61741929
• NM_004361.5:c.51T>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.51T>A​(p.Leu17Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,613,518 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (63 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (52 hom.)
• Consequence: CDH7 NM_004361.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.813
• 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=-0.56).
• BP6: Variant 18-65762893-T-A is Benign according to our data. Variant chr18-65762893-T-A is described in ClinVar as [Benign]. Clinvar id is 782316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.813 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH7	NM_004361.5	c.51T>A	p.Leu17Leu	synonymous_variant	Exon 2 of 12	ENST00000397968.4	NP_004352.2
CDH7	NM_001362438.2	c.51T>A	p.Leu17Leu	synonymous_variant	Exon 2 of 12		NP_001349367.1
CDH7	NM_033646.4	c.51T>A	p.Leu17Leu	synonymous_variant	Exon 2 of 12		NP_387450.1
CDH7	NM_001317214.3	c.51T>A	p.Leu17Leu	synonymous_variant	Exon 2 of 11		NP_001304143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH7	ENST00000397968.4	c.51T>A	p.Leu17Leu	synonymous_variant	Exon 2 of 12	1	NM_004361.5	ENSP00000381058.2
CDH7	ENST00000323011.7	c.51T>A	p.Leu17Leu	synonymous_variant	Exon 2 of 12	1		ENSP00000319166.3
CDH7	ENST00000536984.6	c.51T>A	p.Leu17Leu	synonymous_variant	Exon 2 of 11	1		ENSP00000443030.2
CDH7	ENST00000581601.1	n.-115T>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2099 AN: 152092 Hom.: 60 Cov.: 32

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00862

GnomAD2 exomes AF: 0.00370 AC: 928 AN: 251036 AF XY: 0.00279

Gnomad AFR exome AF: 0.0502

Gnomad AMR exome AF: 0.00238

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00150 AC: 2193 AN: 1461310 Hom.: 52 Cov.: 32 AF XY: 0.00125 AC XY: 906 AN XY: 726960

African (AFR) AF: 0.0523 AC: 1748 AN: 33444

American (AMR) AF: 0.00291 AC: 130 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00232 AC: 13 AN: 5608

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1111770

Other (OTH) AF: 0.00399 AC: 241 AN: 60360

GnomAD4 genome AF: 0.0139 AC: 2117 AN: 152208 Hom.: 63 Cov.: 32 AF XY: 0.0142 AC XY: 1057 AN XY: 74404

African (AFR) AF: 0.0485 AC: 2012 AN: 41508

American (AMR) AF: 0.00497 AC: 76 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68032

Other (OTH) AF: 0.00853 AC: 18 AN: 2110

Alfa AF: 0.00413 Hom.: 2

Bravo AF: 0.0157

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.000119

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

- -

Jul 04, 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	-0.56
CADD	Benign	3.7
DANN	Benign	0.83
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism

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: rs61741929; hg19: chr18-63430129;