chr18-65809574-C-T

Variant names:

• chr18-65809574-C-T
• rs11151216
• NM_004361.5:c.211-130C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004361.5(CDH7):​c.211-130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.983 in 708,406 control chromosomes in the GnomAD database, including 343,149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.94 (68510 hom., cov: 32)
  • Exomes 𝑓: 0.99 (274639 hom.)
• Consequence: CDH7 NM_004361.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0330
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 18-65809574-C-T is Benign according to our data. Variant chr18-65809574-C-T is described in ClinVar as [Benign]. Clinvar id is 1277699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH7	NM_004361.5	c.211-130C>T		intron_variant	Intron 2 of 11	ENST00000397968.4	NP_004352.2
CDH7	NM_001362438.2	c.211-130C>T		intron_variant	Intron 2 of 11		NP_001349367.1
CDH7	NM_033646.4	c.211-130C>T		intron_variant	Intron 2 of 11		NP_387450.1
CDH7	NM_001317214.3	c.211-130C>T		intron_variant	Intron 2 of 10		NP_001304143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH7	ENST00000397968.4	c.211-130C>T		intron_variant	Intron 2 of 11	1	NM_004361.5	ENSP00000381058.2
CDH7	ENST00000323011.7	c.211-130C>T		intron_variant	Intron 2 of 11	1		ENSP00000319166.3
CDH7	ENST00000536984.6	c.211-130C>T		intron_variant	Intron 2 of 10	1		ENSP00000443030.2

Frequencies

GnomAD3 genomes AF: 0.945 AC: 143753 AN: 152150 Hom.: 68459 Cov.: 32

Gnomad AFR AF: 0.808

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.979

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.956

GnomAD4 exome AF: 0.993 AC: 552404 AN: 556140 Hom.: 274639 AF XY: 0.994 AC XY: 288636 AN XY: 290276

African (AFR) AF: 0.811 AC: 11610 AN: 14324

American (AMR) AF: 0.986 AC: 22098 AN: 22404

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 14863 AN: 14872

East Asian (EAS) AF: 1.00 AC: 32378 AN: 32378

South Asian (SAS) AF: 1.00 AC: 48826 AN: 48846

European-Finnish (FIN) AF: 1.00 AC: 36659 AN: 36660

Middle Eastern (MID) AF: 0.989 AC: 2125 AN: 2148

European-Non Finnish (NFE) AF: 0.999 AC: 354601 AN: 354824

Other (OTH) AF: 0.985 AC: 29244 AN: 29684

GnomAD4 genome AF: 0.945 AC: 143861 AN: 152266 Hom.: 68510 Cov.: 32 AF XY: 0.946 AC XY: 70420 AN XY: 74448

African (AFR) AF: 0.809 AC: 33572 AN: 41506

American (AMR) AF: 0.979 AC: 14980 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3468 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5166 AN: 5166

South Asian (SAS) AF: 0.999 AC: 4822 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10628 AN: 10628

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67999 AN: 68046

Other (OTH) AF: 0.957 AC: 2024 AN: 2116

Alfa AF: 0.978 Hom.: 28453

Bravo AF: 0.937

Asia WGS AF: 0.988 AC: 3437 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 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	-0.73
CADD	Benign	6.4
DANN	Benign	0.62
PhyloP100		0.033
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: rs11151216; hg19: chr18-63476810;