rs1469025932

Variant names:

• chr10-84194810-G-A
• rs1469025932
• NM_033100.4:c.50G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-84194810-G-A
• chr10-84194810-G-C
• chr10-84194810-G-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.50G>A​(p.Cys17Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDHR1 NM_033100.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13
• 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=0.16418216).

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.50G>A	p.Cys17Tyr	missense	Exon 1 of 17	NP_149091.1	Q96JP9-1
	CDHR1	NM_001171971.3		c.50G>A	p.Cys17Tyr	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.50G>A	p.Cys17Tyr	missense	Exon 1 of 17	ENSP00000485478.1	Q96JP9-1
	CDHR1	ENST00000332904.7	TSL:1	c.50G>A	p.Cys17Tyr	missense	Exon 1 of 17	ENSP00000331063.3	Q96JP9-2
	CDHR1	ENST00000926454.1		c.50G>A	p.Cys17Tyr	missense	Exon 1 of 16	ENSP00000596513.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1380648 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 681352

African (AFR) AF: 0.00 AC: 0 AN: 31488

American (AMR) AF: 0.00 AC: 0 AN: 35640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25102

East Asian (EAS) AF: 0.00 AC: 0 AN: 35696

South Asian (SAS) AF: 0.00 AC: 0 AN: 79096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4372

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077990

Other (OTH) AF: 0.00 AC: 0 AN: 57674

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.54	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.1
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.099
Sift	Benign	0.32	T
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.46		Loss of catalytic residue at L18 (P = 0.0205)
MVP		0.24
ClinPred		0.17	T
GERP RS		3.1
PromoterAI		0.022	Neutral
Varity_R		0.10
gMVP		0.38
Mutation Taster		=95/5	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: rs1469025932; hg19: chr10-85954566;