10-84203068-C-T

Position:

chr10-84203068-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033100.4(CDHR1):c.728C>T(p.Ala243Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00521 in 1,614,188 control chromosomes in the GnomAD database, including 341 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 162 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 179 hom. )

Consequence

CDHR1
NM_033100.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.40

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058300495).

BP6

Variant 10-84203068-C-T is Benign according to our data. Variant chr10-84203068-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDHR1	NM_033100.4 linkuse as main transcript	c.728C>T	p.Ala243Val	missense_variant	8/17	ENST00000623527.4	NP_149091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDHR1	ENST00000623527.4 linkuse as main transcript	c.728C>T	p.Ala243Val	missense_variant	8/17	1	NM_033100.4	ENSP00000485478	P2	Q96JP9-1
CDHR1	ENST00000332904.7 linkuse as main transcript	c.728C>T	p.Ala243Val	missense_variant	8/17	1		ENSP00000331063	A2	Q96JP9-2
CDHR1	ENST00000372117.6 linkuse as main transcript	c.110C>T	p.Ala37Val	missense_variant	2/10	2		ENSP00000361189

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

3944

AN:

152196

Hom.:

162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0885

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.000926

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.00717

AC:

1802

AN:

251476

Hom.:

AF XY:

0.00517

AC XY:

703

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.0926

Gnomad AMR exome

AF:

0.00543

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000677

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00305

AC:

4462

AN:

1461874

Hom.:

179

Cov.:

AF XY:

0.00270

AC XY:

1960

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0956

Gnomad4 AMR exome

AF:

0.00628

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000335

Gnomad4 OTH exome

AF:

0.00806

GnomAD4 genome

AF:

0.0260

AC:

3953

AN:

152314

Hom.:

162

Cov.:

AF XY:

0.0248

AC XY:

1847

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0885

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000926

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.00566

Hom.:

Bravo

AF:

0.0289

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0912

AC:

402

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00863

AC:

1048

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000948

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 20, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Cone-Rod Dystrophy, Recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.49

LIST_S2

Uncertain

0.95

D;D

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.0

.;N

REVEL

Benign

0.032

Sift

Uncertain

0.012

.;D

Sift4G

Uncertain

0.027

D;T

Polyphen

0.072

B;B

Vest4

0.36

MVP

0.21

ClinPred

0.011

GERP RS

0.84

Varity_R

0.072

gMVP

0.52

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over