rs4933975

Positions:

• chr10-84200639-A-G
• chr10-84200639-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_033100.4(CDHR1):​c.477A>G​(p.Ala159=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.03

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]

ACMG classification

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/exons	MANE	UniProt
CDHR1	NM_033100.4	c.477A>G	p.Ala159=	synonymous_variant	6/17	ENST00000623527.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDHR1	ENST00000623527.4	c.477A>G	p.Ala159=	synonymous_variant	6/17	1	NM_033100.4	P2
CDHR1	ENST00000332904.7	c.477A>G	p.Ala159=	synonymous_variant	6/17	1		A2

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79046 AN: 151964 Hom.: 21379 Cov.: 32

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

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.: 38 AF XY: 0.459 AC XY: 332768 AN XY: 724874

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.: 32 AF XY: 0.518 AC XY: 38490 AN XY: 74340

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:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 26, 2018	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. -

Cone-Rod Dystrophy, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Cone-rod dystrophy 15 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

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

Other links and lift over

dbSNP: rs4933975; hg19: chr10-85960395; COSMIC: COSV60561610; COSMIC: COSV60561610;