Genetic Variant CDH7:c.211-130C>T (chr18-65809574-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0330

Publications

1 publications found

Variant links:

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]

CDH7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004361.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDH7	NM_004361.5	MANE Select	c.211-130C>T	intron	N/A	NP_004352.2
CDH7	NM_001362438.2		c.211-130C>T	intron	N/A	NP_001349367.1	Q9ULB5
CDH7	NM_033646.4		c.211-130C>T	intron	N/A	NP_387450.1	Q9ULB5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDH7	ENST00000397968.4	TSL:1 MANE Select	c.211-130C>T	intron	N/A	ENSP00000381058.2	Q9ULB5
CDH7	ENST00000323011.7	TSL:1	c.211-130C>T	intron	N/A	ENSP00000319166.3	Q9ULB5
CDH7	ENST00000536984.6	TSL:1	c.211-130C>T	intron	N/A	ENSP00000443030.2	F5H5X9

Frequencies

GnomAD3 genomes

AF:

0.945

AC:

143753

AN:

152150

Hom.:

68459

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

163

326

489

652

815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2998

5996

8994

11992

14990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.945

AC:

143861

AN:

152266

Hom.:

68510

Cov.:

AF XY:

0.946

AC XY:

70420

AN XY:

74448

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

341

682

1024

1365

1706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.978

Hom.:

28453

Bravo

AF:

0.937

Asia WGS

AF:

0.988

AC:

3437

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.4

(source)

DANN

Benign

0.62

PhyloP100

0.033

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over