dbSNP rs6967330: CDHR3:p.Cys529Tyr (chr7-106018005-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_152750.5(CDHR3):c.1586G>A(p.Cys529Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,611,648 control chromosomes in the GnomAD database, including 27,565 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3386 hom., cov: 31)

Exomes 𝑓: 0.18 ( 24179 hom. )

Consequence

CDHR3
NM_152750.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.35

Publications

132 publications found

Variant links:

Genes affected

CDHR3 (HGNC:26308): (cadherin related family member 3) Predicted to enable cadherin binding activity and calcium ion binding activity. Predicted to be involved in calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules; cell morphogenesis; and cell-cell junction organization. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CDHR3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0056328475).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDHR3	NM_152750.5 link	c.1586G>A	p.Cys529Tyr	missense_variant	Exon 12 of 19	ENST00000317716.14	NP_689963.2	Q6ZTQ4-1
CDHR3	NM_001301161.2 link	c.1322G>A	p.Cys441Tyr	missense_variant	Exon 11 of 18		NP_001288090.1	Q6ZTQ4E7EQG5B7Z8X2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDHR3	ENST00000317716.14 link	c.1586G>A	p.Cys529Tyr	missense_variant	Exon 12 of 19	1	NM_152750.5	ENSP00000325954.9		Q6ZTQ4-1

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30769

AN:

151900

Hom.:

3378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.0718

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.302

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.210

GnomAD2 exomes

AF:

0.185

AC:

46124

AN:

248940

AF XY:

0.189

show subpopulations

Gnomad AFR exome

AF:

0.262

Gnomad AMR exome

AF:

0.134

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.0704

Gnomad FIN exome

AF:

0.288

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.187

GnomAD4 exome

AF:

0.176

AC:

257227

AN:

1459630

Hom.:

24179

Cov.:

AF XY:

0.179

AC XY:

129630

AN XY:

726206

show subpopulations

African (AFR)

AF:

0.265

AC:

8877

AN:

33446

American (AMR)

AF:

0.139

AC:

6210

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

5199

AN:

26124

East Asian (EAS)

AF:

0.0814

AC:

3231

AN:

39690

South Asian (SAS)

AF:

0.224

AC:

19285

AN:

86130

European-Finnish (FIN)

AF:

0.283

AC:

15090

AN:

53378

Middle Eastern (MID)

AF:

0.286

AC:

1646

AN:

5760

European-Non Finnish (NFE)

AF:

0.168

AC:

186692

AN:

1110088

Other (OTH)

AF:

0.182

AC:

10997

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

11052

22105

33157

44210

55262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6692

13384

20076

26768

33460

<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:

0.203

AC:

30826

AN:

152018

Hom.:

3386

Cov.:

AF XY:

0.207

AC XY:

15406

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.260

AC:

10770

AN:

41428

American (AMR)

AF:

0.172

AC:

2628

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

654

AN:

3470

East Asian (EAS)

AF:

0.0720

AC:

371

AN:

5156

South Asian (SAS)

AF:

0.205

AC:

987

AN:

4816

European-Finnish (FIN)

AF:

0.302

AC:

3184

AN:

10560

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.170

AC:

11586

AN:

67980

Other (OTH)

AF:

0.217

AC:

458

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1196

2391

3587

4782

5978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<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:

0.178

Hom.:

9895

Bravo

AF:

0.198

TwinsUK

AF:

0.170

AC:

630

ALSPAC

AF:

0.165

AC:

636

ESP6500AA

AF:

0.249

AC:

967

ESP6500EA

AF:

0.169

AC:

1405

ExAC

AF:

0.189

AC:

22787

Asia WGS

AF:

0.197

AC:

686

AN:

3478

EpiCase

AF:

0.177

EpiControl

AF:

0.178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.7

(source)

DANN

Benign

0.49

DEOGEN2

Benign

0.0030

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.20

T;T

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.4

N;.

PhyloP100

3.4

PrimateAI

Benign

0.27

PROVEAN

Benign

4.5

N;N

REVEL

Benign

0.14

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.029

MPC

0.048

ClinPred

0.0026

GERP RS

4.4

Varity_R

0.056

gMVP

0.28

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