rs4933975

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_033100.4(CDHR1):c.477A>G(p.Ala159Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 1,609,788 control chromosomes in the GnomAD database, including 178,669 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21428 hom., cov: 32)

Exomes 𝑓: 0.46 ( 157241 hom. )

Consequence

CDHR1
NM_033100.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.03

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 10-84200639-A-G is Benign according to our data. Variant chr10-84200639-A-G is described in ClinVar as [Benign]. Clinvar id is 262215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-84200639-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDHR1	NM_033100.4 link	c.477A>G	p.Ala159Ala	synonymous_variant	Exon 6 of 17	ENST00000623527.4	NP_149091.1	Q96JP9-1F1T0L2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDHR1	ENST00000623527.4 link	c.477A>G	p.Ala159Ala	synonymous_variant	Exon 6 of 17	1	NM_033100.4	ENSP00000485478.1		Q96JP9-1
CDHR1	ENST00000332904.7 link	c.477A>G	p.Ala159Ala	synonymous_variant	Exon 6 of 17	1		ENSP00000331063.3		Q96JP9-2

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

79046

AN:

151964

Hom.:

21379

Cov.:

show subpopulations

Gnomad AFR

AF:

0.687

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.528

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.389

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.442

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.451

Gnomad OTH

AF:

0.503

GnomAD3 exomes

AF:

0.474

AC:

116518

AN:

245878

Hom.:

28226

AF XY:

0.466

AC XY:

61936

AN XY:

132798

show subpopulations

Gnomad AFR exome

AF:

0.688

Gnomad AMR exome

AF:

0.556

Gnomad ASJ exome

AF:

0.456

Gnomad EAS exome

AF:

0.380

Gnomad SAS exome

AF:

0.435

Gnomad FIN exome

AF:

0.445

Gnomad NFE exome

AF:

0.453

Gnomad OTH exome

AF:

0.451

GnomAD4 exome

AF:

0.462

AC:

672914

AN:

1457706

Hom.:

157241

Cov.:

AF XY:

0.459

AC XY:

332768

AN XY:

724874

show subpopulations

Gnomad4 AFR exome

AF:

0.693

Gnomad4 AMR exome

AF:

0.554

Gnomad4 ASJ exome

AF:

0.465

Gnomad4 EAS exome

AF:

0.346

Gnomad4 SAS exome

AF:

0.437

Gnomad4 FIN exome

AF:

0.450

Gnomad4 NFE exome

AF:

0.457

Gnomad4 OTH exome

AF:

0.469

GnomAD4 genome

AF:

0.521

AC:

79159

AN:

152082

Hom.:

21428

Cov.:

AF XY:

0.518

AC XY:

38490

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.687

Gnomad4 AMR

AF:

0.528

Gnomad4 ASJ

AF:

0.473

Gnomad4 EAS

AF:

0.389

Gnomad4 SAS

AF:

0.440

Gnomad4 FIN

AF:

0.442

Gnomad4 NFE

AF:

0.451

Gnomad4 OTH

AF:

0.508

Alfa

AF:

0.469

Hom.:

20992

Bravo

AF:

0.537

Asia WGS

AF:

0.471

AC:

1640

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cone-Rod Dystrophy, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cone-rod dystrophy 15

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.016

DANN

Benign

0.29

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