rs766698407

Variant names:

• chr10-84194773-C-G
• rs766698407
• NM_033100.4:c.13C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-84194773-C-G
• chr10-84194773-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033100.4(CDHR1):​c.13C>G​(p.Arg5Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,370,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R5W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: CDHR1 NM_033100.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 0 publications found

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]

CDHR1 Gene-Disease associations (from GenCC):

• cone-rod dystrophy 15

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• retinitis pigmentosa 65

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08083281).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033100.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDHR1	NM_033100.4	MANE Select	c.13C>G	p.Arg5Gly	missense	Exon 1 of 17	NP_149091.1	Q96JP9-1
	CDHR1	NM_001171971.3		c.13C>G	p.Arg5Gly	missense	Exon 1 of 17	NP_001165442.1	Q96JP9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDHR1	ENST00000623527.4	TSL:1 MANE Select	c.13C>G	p.Arg5Gly	missense	Exon 1 of 17	ENSP00000485478.1	Q96JP9-1
	CDHR1	ENST00000332904.7	TSL:1	c.13C>G	p.Arg5Gly	missense	Exon 1 of 17	ENSP00000331063.3	Q96JP9-2
	CDHR1	ENST00000926454.1		c.13C>G	p.Arg5Gly	missense	Exon 1 of 16	ENSP00000596513.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.30e-7 AC: 1 AN: 1370660 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 676060

African (AFR) AF: 0.0000336 AC: 1 AN: 29786

American (AMR) AF: 0.00 AC: 0 AN: 34978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24694

East Asian (EAS) AF: 0.00 AC: 0 AN: 34582

South Asian (SAS) AF: 0.00 AC: 0 AN: 78256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4062

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073738

Other (OTH) AF: 0.00 AC: 0 AN: 57150

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Benign	0.68
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.4
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.099
Sift	Benign	0.34	T
Sift4G	Benign	0.12	T
Polyphen		0.0030	B
Vest4		0.17
MutPred		0.51		Loss of helix (P = 0.0104)
MVP		0.13
ClinPred		0.072	T
GERP RS		2.1
PromoterAI		-0.062	Neutral
Varity_R		0.043
gMVP		0.22
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs766698407; hg19: chr10-85954529;