Variant rs6967330 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CDHR3	NM_152750.5 linkuse as main transcript	c.1586G>A	p.Cys529Tyr	missense_variant	12/19	ENST00000317716.14	NP_689963.2
CDHR3	NM_001301161.2 linkuse as main transcript	c.1322G>A	p.Cys441Tyr	missense_variant	11/18		NP_001288090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDHR3	ENST00000317716.14 linkuse as main transcript	c.1586G>A	p.Cys529Tyr	missense_variant	12/19	1	NM_152750.5	ENSP00000325954	P1	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

GnomAD3 exomes

AF:

0.185

AC:

46124

AN:

248940

Hom.:

4761

AF XY:

0.189

AC XY:

25473

AN XY:

135062

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 SAS exome

AF:

0.224

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

Gnomad4 AFR exome

AF:

0.265

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.199

Gnomad4 EAS exome

AF:

0.0814

Gnomad4 SAS exome

AF:

0.224

Gnomad4 FIN exome

AF:

0.283

Gnomad4 NFE exome

AF:

0.168

Gnomad4 OTH exome

AF:

0.182

GnomAD4 genome

AF:

0.203

AC:

30826

AN:

152018

Hom.:

3386

Cov.:

AF XY:

0.207

AC XY:

15406

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.260

Gnomad4 AMR

AF:

0.172

Gnomad4 ASJ

AF:

0.188

Gnomad4 EAS

AF:

0.0720

Gnomad4 SAS

AF:

0.205

Gnomad4 FIN

AF:

0.302

Gnomad4 NFE

AF:

0.170

Gnomad4 OTH

AF:

0.217

Alfa

AF:

0.174

Hom.:

4867

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

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;.

MutationTaster

Benign

1.0

P;P;P;P

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over