rs10749482

Positions:

• chr10-84212287-A-G

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.1662A>G​(p.Glu554=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,613,930 control chromosomes in the GnomAD database, including 89,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (15308 hom., cov: 33)
  • Exomes 𝑓: 0.31 (74530 hom.)
• Consequence: CDHR1 NM_033100.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.341

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=-0.59).
• BP6: Variant 10-84212287-A-G is Benign according to our data. Variant chr10-84212287-A-G is described in ClinVar as [Benign]. Clinvar id is 262210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-84212287-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.341 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDHR1	NM_033100.4	c.1662A>G	p.Glu554=	synonymous_variant	15/17	ENST00000623527.4	NP_149091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDHR1	ENST00000623527.4	c.1662A>G	p.Glu554=	synonymous_variant	15/17	1	NM_033100.4	ENSP00000485478	P2
CDHR1	ENST00000332904.7	c.1662A>G	p.Glu554=	synonymous_variant	15/17	1		ENSP00000331063	A2
CDHR1	ENST00000372117.6	c.879A>G	p.Glu293=	synonymous_variant	8/10	2		ENSP00000361189
CDHR1	ENST00000622973.1	c.396A>G	p.Glu132=	synonymous_variant, NMD_transcript_variant	4/6	5		ENSP00000485151

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63203 AN: 152002 Hom.: 15275 Cov.: 33

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.375

GnomAD3 exomes AF: 0.353 AC: 88758 AN: 251484 Hom.: 17291 AF XY: 0.342 AC XY: 46428 AN XY: 135918

Gnomad AFR exome AF: 0.685

Gnomad AMR exome AF: 0.463

Gnomad ASJ exome AF: 0.333

Gnomad EAS exome AF: 0.249

Gnomad SAS exome AF: 0.332

Gnomad FIN exome AF: 0.372

Gnomad NFE exome AF: 0.294

Gnomad OTH exome AF: 0.315

GnomAD4 exome AF: 0.310 AC: 452938 AN: 1461810 Hom.: 74530 Cov.: 43 AF XY: 0.308 AC XY: 224315 AN XY: 727206

Gnomad4 AFR exome AF: 0.702

Gnomad4 AMR exome AF: 0.458

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.239

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.370

Gnomad4 NFE exome AF: 0.289

Gnomad4 OTH exome AF: 0.325

GnomAD4 genome AF: 0.416 AC: 63296 AN: 152120 Hom.: 15308 Cov.: 33 AF XY: 0.417 AC XY: 31000 AN XY: 74366

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.376

Alfa AF: 0.321 Hom.: 12747

Bravo AF: 0.432

Asia WGS AF: 0.340 AC: 1183 AN: 3478

EpiCase AF: 0.286

EpiControl AF: 0.287

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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	-	- -

not provided Benign:3

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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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	-0.59
CADD	Benign	4.6
DANN	Benign	0.47

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: rs10749482; hg19: chr10-85972043; COSMIC: COSV60565208; COSMIC: COSV60565208;