Genetic Variant CDH6:c.1000-16C>T (chr5-31305158-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004932.4(CDH6):c.1000-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 1,597,944 control chromosomes in the GnomAD database, including 3,336 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.058 ( 269 hom., cov: 32)

Exomes 𝑓: 0.062 ( 3067 hom. )

Consequence

CDH6
NM_004932.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.436

Publications

5 publications found

Variant links:

Genes affected

CDH6 (HGNC:1765): (cadherin 6) This gene encodes a member of the cadherin superfamily. Cadherins are membrane glycoproteins that mediate homophilic cell-cell adhesion and play critical roles in cell differentiation and morphogenesis. The encoded protein is a type II cadherin and may play a role in kidney development as well as endometrium and placenta formation. Decreased expression of this gene may be associated with tumor growth and metastasis. [provided by RefSeq, May 2011]

CDH6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CDH6	NM_004932.4 link	c.1000-16C>T	intron_variant	Intron 6 of 11	ENST00000265071.3	NP_004923.1	P55285-1
CDH6	NM_001362435.2 link	c.1000-16C>T	intron_variant	Intron 6 of 10		NP_001349364.1
CDH6	XM_011513921.4 link	c.1000-16C>T	intron_variant	Intron 6 of 11		XP_011512223.1	P55285-1
CDH6	XM_047416591.1 link	c.1000-16C>T	intron_variant	Intron 6 of 11		XP_047272547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH6	ENST00000265071.3 link	c.1000-16C>T		intron_variant	Intron 6 of 11	2	NM_004932.4	ENSP00000265071.2		P55285-1
CDH6	ENST00000514738.5 link	c.835-16C>T		intron_variant	Intron 6 of 10	1		ENSP00000424843.1		D6RF86

Frequencies

GnomAD3 genomes

AF:

0.0579

AC:

8799

AN:

152088

Hom.:

270

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0539

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0420

Gnomad ASJ

AF:

0.0510

Gnomad EAS

AF:

0.0503

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.0636

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0601

Gnomad OTH

AF:

0.0516

GnomAD2 exomes

AF:

0.0610

AC:

14706

AN:

241110

AF XY:

0.0645

show subpopulations

Gnomad AFR exome

AF:

0.0542

Gnomad AMR exome

AF:

0.0286

Gnomad ASJ exome

AF:

0.0459

Gnomad EAS exome

AF:

0.0549

Gnomad FIN exome

AF:

0.0594

Gnomad NFE exome

AF:

0.0623

Gnomad OTH exome

AF:

0.0547

GnomAD4 exome

AF:

0.0619

AC:

89480

AN:

1445738

Hom.:

3067

Cov.:

AF XY:

0.0632

AC XY:

45336

AN XY:

717532

show subpopulations

African (AFR)

AF:

0.0555

AC:

1807

AN:

32566

American (AMR)

AF:

0.0297

AC:

1254

AN:

42172

Ashkenazi Jewish (ASJ)

AF:

0.0463

AC:

1175

AN:

25354

East Asian (EAS)

AF:

0.0440

AC:

1736

AN:

39466

South Asian (SAS)

AF:

0.105

AC:

8802

AN:

83686

European-Finnish (FIN)

AF:

0.0612

AC:

3250

AN:

53126

Middle Eastern (MID)

AF:

0.0654

AC:

371

AN:

5672

European-Non Finnish (NFE)

AF:

0.0612

AC:

67594

AN:

1104054

Other (OTH)

AF:

0.0585

AC:

3491

AN:

59642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

3608

7216

10823

14431

18039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2556

5112

7668

10224

12780

<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:

0.0579

AC:

8809

AN:

152206

Hom.:

269

Cov.:

AF XY:

0.0593

AC XY:

4416

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0541

AC:

2249

AN:

41536

American (AMR)

AF:

0.0419

AC:

641

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0510

AC:

177

AN:

3468

East Asian (EAS)

AF:

0.0497

AC:

257

AN:

5174

South Asian (SAS)

AF:

0.110

AC:

529

AN:

4828

European-Finnish (FIN)

AF:

0.0636

AC:

674

AN:

10600

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0601

AC:

4088

AN:

67998

Other (OTH)

AF:

0.0511

AC:

108

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

458

916

1374

1832

2290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0566

Hom.:

484

Bravo

AF:

0.0535

Asia WGS

AF:

0.0820

AC:

284

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.68

(source)

DANN

Benign

0.54

PhyloP100

0.44

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over