Genetic Variant NM_033100.4:c.13C>G (chr10-84194773-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.37

Publications

0 publications found

Variant links:

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

CDHR1 links:

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ACMG classification

Classification was made for transcript

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

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.:

GnomAD4 exome

AF:

7.30e-7

AC:

AN:

1370660

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

676060

show subpopulations

African (AFR)

AF:

0.0000336

AC:

AN:

29786

American (AMR)

AF:

0.00

AC:

AN:

34978

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24694

East Asian (EAS)

AF:

0.00

AC:

AN:

34582

South Asian (SAS)

AF:

0.00

AC:

AN:

78256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4062

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1073738

Other (OTH)

AF:

0.00

AC:

AN:

57150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

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

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.13

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.37

M_CAP

Benign

0.078

MetaRNN

Benign

0.081

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

1.4

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.3

REVEL

Benign

0.099

Sift

Benign

0.34

Sift4G

Benign

0.12

Polyphen

0.0030

Vest4

0.17

MutPred

0.51

Loss of helix (P = 0.0104)

MVP

0.13

ClinPred

0.072

GERP RS

2.1

PromoterAI

-0.062

Neutral

(source)

Varity_R

0.043

gMVP

0.22

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over