10-84214475-C-T

Position:

• chr10-84214475-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000623527.4(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 ENST00000623527.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 5.83

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 -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 [Likely_benign]. Clinvar id is 262213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-84214475-C-T is described in Lovd as [Likely_benign].
• 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 119 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDHR1	NM_033100.4	c.2434C>T	p.Pro812Ser	missense_variant	17/17	ENST00000623527.4	NP_149091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDHR1	ENST00000623527.4	c.2434C>T	p.Pro812Ser	missense_variant	17/17	1	NM_033100.4	ENSP00000485478	P2

Frequencies

GnomAD3 genomes AF: 0.0311 AC: 4726 AN: 152172 Hom.: 119 Cov.: 33

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

GnomAD3 exomes AF: 0.0309 AC: 7640 AN: 247434 Hom.: 204 AF XY: 0.0308 AC XY: 4135 AN XY: 134172

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 SAS exome AF: 0.00938

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.: 33 AF XY: 0.0379 AC XY: 27469 AN XY: 725382

Gnomad4 AFR exome AF: 0.00514

Gnomad4 AMR exome AF: 0.0113

Gnomad4 ASJ exome AF: 0.0222

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0106

Gnomad4 FIN exome AF: 0.0757

Gnomad4 NFE exome AF: 0.0434

Gnomad4 OTH exome AF: 0.0296

GnomAD4 genome AF: 0.0310 AC: 4724 AN: 152290 Hom.: 119 Cov.: 33 AF XY: 0.0323 AC XY: 2402 AN XY: 74470

Gnomad4 AFR AF: 0.00616

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00994

Gnomad4 FIN AF: 0.0807

Gnomad4 NFE AF: 0.0449

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0334 Hom.: 66

Bravo AF: 0.0247

TwinsUK AF: 0.0442 AC: 164

ALSPAC AF: 0.0361 AC: 139

ESP6500AA AF: 0.00726 AC: 32

ESP6500EA AF: 0.0399 AC: 343

ExAC AF: 0.0319 AC: 3874

Asia WGS AF: 0.00549 AC: 19 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

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	This variant is associated with the following publications: (PMID: 29248581) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 01, 2015	- -
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	0.28
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.0034	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.60	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.12
ClinPred		0.016	T
GERP RS		5.3
Varity_R		0.51
gMVP		0.48

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: rs45584033; hg19: chr10-85974231; COSMIC: COSV60559535; COSMIC: COSV60559535;