rs7086200

Positions:

• chr10-84203068-C-T

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.728C>T​(p.Ala243Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00521 in 1,614,188 control chromosomes in the GnomAD database, including 341 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (162 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (179 hom.)
• Consequence: CDHR1 NM_033100.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.40

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=0.0058300495).
• BP6: Variant 10-84203068-C-T is Benign according to our data. Variant chr10-84203068-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDHR1	NM_033100.4	c.728C>T	p.Ala243Val	missense_variant	8/17	ENST00000623527.4	NP_149091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDHR1	ENST00000623527.4	c.728C>T	p.Ala243Val	missense_variant	8/17	1	NM_033100.4	ENSP00000485478	P2
CDHR1	ENST00000332904.7	c.728C>T	p.Ala243Val	missense_variant	8/17	1		ENSP00000331063	A2
CDHR1	ENST00000372117.6	c.110C>T	p.Ala37Val	missense_variant	2/10	2		ENSP00000361189

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 3944 AN: 152196 Hom.: 162 Cov.: 33

Gnomad AFR AF: 0.0885

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: 0.00717 AC: 1802 AN: 251476 Hom.: 76 AF XY: 0.00517 AC XY: 703 AN XY: 135918

Gnomad AFR exome AF: 0.0926

Gnomad AMR exome AF: 0.00543

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000677

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00305 AC: 4462 AN: 1461874 Hom.: 179 Cov.: 32 AF XY: 0.00270 AC XY: 1960 AN XY: 727236

Gnomad4 AFR exome AF: 0.0956

Gnomad4 AMR exome AF: 0.00628

Gnomad4 ASJ exome AF: 0.000306

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000290

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000335

Gnomad4 OTH exome AF: 0.00806

GnomAD4 genome AF: 0.0260 AC: 3953 AN: 152314 Hom.: 162 Cov.: 33 AF XY: 0.0248 AC XY: 1847 AN XY: 74478

Gnomad4 AFR AF: 0.0885

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: 0.00566 Hom.: 56

Bravo AF: 0.0289

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0912 AC: 402

ESP6500EA AF: 0.00198 AC: 17

ExAC AF: 0.00863 AC: 1048

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.000948

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 20, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

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	0.095
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.49	N
LIST_S2	Uncertain	0.95	D;D
MetaRNN	Benign	0.0058	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.0	.;N
REVEL	Benign	0.032
Sift	Uncertain	0.012	.;D
Sift4G	Uncertain	0.027	D;T
Polyphen		0.072	B;B
Vest4		0.36
MVP		0.21
ClinPred		0.011	T
GERP RS		0.84
Varity_R		0.072
gMVP		0.52

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: rs7086200; hg19: chr10-85962824;