rs74145715

chr10-84200648-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033100.4(CDHR1):c.486G>C(p.Arg162Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00519 in 1,612,546 control chromosomes in the GnomAD database, including 338 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (158 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (180 hom.)
• Consequence: CDHR1 NM_033100.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.56

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=0.00458923).
• BP6: Variant 10-84200648-G-C is Benign according to our data. Variant chr10-84200648-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 262216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDHR1	NM_033100.4	c.486G>C	p.Arg162Ser	missense_variant	6/17	ENST00000623527.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDHR1	ENST00000623527.4	c.486G>C	p.Arg162Ser	missense_variant	6/17	1	NM_033100.4	P2
CDHR1	ENST00000332904.7	c.486G>C	p.Arg162Ser	missense_variant	6/17	1		A2

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3925 AN: 152126 Hom.: 158 Cov.: 32

Gnomad AFR AF: 0.0882

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: 0.00679 AC: 1680 AN: 247330 Hom.: 70 AF XY: 0.00486 AC XY: 649 AN XY: 133672

Gnomad AFR exome AF: 0.0892

Gnomad AMR exome AF: 0.00525

Gnomad ASJ exome AF: 0.000903

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000667

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000660

Gnomad OTH exome AF: 0.00347

GnomAD4 exome AF: 0.00304 AC: 4443 AN: 1460302 Hom.: 180 Cov.: 32 AF XY: 0.00268 AC XY: 1949 AN XY: 726242

Gnomad4 AFR exome AF: 0.0955

Gnomad4 AMR exome AF: 0.00617

Gnomad4 ASJ exome AF: 0.000307

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000280

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000333

Gnomad4 OTH exome AF: 0.00802

GnomAD4 genome AF: 0.0258 AC: 3934 AN: 152244 Hom.: 158 Cov.: 32 AF XY: 0.0247 AC XY: 1838 AN XY: 74454

Gnomad4 AFR AF: 0.0881

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: 0.00433 Hom.: 14

Bravo AF: 0.0289

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0906 AC: 399

ESP6500EA AF: 0.00198 AC: 17

ExAC AF: 0.00818 AC: 993

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 20, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -

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	0.19
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	19
Dann	Benign	0.96
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.63
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.95	D;D
MetaRNN	Benign	0.0046	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.48	N;N
MutationTaster	Benign	0.22	P;P
PrimateAI	Benign	0.25	T
Sift4G	Benign	0.12	T;T
Polyphen		0.025	B;B
Vest4		0.23
MutPred		0.54		Gain of glycosylation at R162 (P = 0.0326);Gain of glycosylation at R162 (P = 0.0326);
MVP		0.20
ClinPred		0.0042	T
GERP RS		2.4
Varity_R		0.099
gMVP		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: rs74145715; hg19: chr10-85960404;