10-84214475-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_033100.4(CDHR1):c.2434C>T(p.Pro812Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0377 in 1,610,018 control chromosomes in the GnomAD database, including 1,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 119 hom., cov: 33)

Exomes 𝑓: 0.038 ( 1333 hom. )

Consequence

CDHR1
NM_033100.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 5.83

Publications

12 publications found

Variant links:

Genes affected

CDHR1 (HGNC:14550): (cadherin related family member 1) This gene belongs to the cadherin superfamily of calcium-dependent cell adhesion molecules. The encoded protein is a photoreceptor-specific cadherin that plays a role in outer segment disc morphogenesis. Mutations in this gene are associated with inherited retinal dystrophies. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2013]

CDHR1 Gene-Disease associations (from GenCC):

cone-rod dystrophy 15
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CDHR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034305751).

BP6

Variant 10-84214475-C-T is Benign according to our data. Variant chr10-84214475-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.031 (4724/152290) while in subpopulation NFE AF = 0.0449 (3056/68016). AF 95% confidence interval is 0.0436. There are 119 homozygotes in GnomAd4. There are 2402 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 119 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDHR1	NM_033100.4 link	c.2434C>T	p.Pro812Ser	missense_variant	Exon 17 of 17	ENST00000623527.4	NP_149091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDHR1	ENST00000623527.4 link	c.2434C>T	p.Pro812Ser	missense_variant	Exon 17 of 17	1	NM_033100.4	ENSP00000485478.1

Frequencies

GnomAD3 genomes

AF:

0.0311

AC:

4726

AN:

152172

Hom.:

119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00618

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.0169

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00993

Gnomad FIN

AF:

0.0807

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0449

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.0309

AC:

7640

AN:

247434

AF XY:

0.0308

show subpopulations

Gnomad AFR exome

AF:

0.00561

Gnomad AMR exome

AF:

0.0108

Gnomad ASJ exome

AF:

0.0223

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0793

Gnomad NFE exome

AF:

0.0447

Gnomad OTH exome

AF:

0.0270

GnomAD4 exome

AF:

0.0384

AC:

56026

AN:

1457728

Hom.:

1333

Cov.:

AF XY:

0.0379

AC XY:

27469

AN XY:

725382

show subpopulations

African (AFR)

AF:

0.00514

AC:

172

AN:

33454

American (AMR)

AF:

0.0113

AC:

503

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.0222

AC:

580

AN:

26070

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.0106

AC:

918

AN:

86240

European-Finnish (FIN)

AF:

0.0757

AC:

3774

AN:

49858

Middle Eastern (MID)

AF:

0.00624

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0434

AC:

48258

AN:

1111648

Other (OTH)

AF:

0.0296

AC:

1785

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

3414

6828

10241

13655

17069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1720

3440

5160

6880

8600

<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:

0.0310

AC:

4724

AN:

152290

Hom.:

119

Cov.:

AF XY:

0.0323

AC XY:

2402

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00616

AC:

256

AN:

41574

American (AMR)

AF:

0.0169

AC:

258

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0222

AC:

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5172

South Asian (SAS)

AF:

0.00994

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0807

AC:

857

AN:

10622

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0449

AC:

3056

AN:

68016

Other (OTH)

AF:

0.0223

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

244

488

731

975

1219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0385

Hom.:

273

Bravo

AF:

0.0247

TwinsUK

AF:

0.0442

AC:

164

ALSPAC

AF:

0.0361

AC:

139

ESP6500AA

AF:

0.00726

AC:

ESP6500EA

AF:

0.0399

AC:

343

ExAC

AF:

0.0319

AC:

3874

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0369

EpiControl

AF:

0.0364

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 30, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29248581) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cone-Rod Dystrophy, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0034

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.3

PhyloP100

5.8

PrimateAI

Uncertain

0.60

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.12

ClinPred

0.016

GERP RS

5.3

Varity_R

0.51

gMVP

0.48

Mutation Taster

=40/60

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over