10-84200393-C-A

Variant names:

• chr10-84200393-C-A
• rs10788333
• NM_033100.4:c.439-208C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033100.4(CDHR1):​c.439-208C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,840 control chromosomes in the GnomAD database, including 21,159 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (21159 hom., cov: 31)
• Consequence: CDHR1 NM_033100.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.42
• Publications: 7 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• cone-rod dystrophy

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDHR1	NM_033100.4	MANE Select	c.439-208C>A		intron	N/A	NP_149091.1
	CDHR1	NM_001171971.3		c.439-208C>A		intron	N/A	NP_001165442.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDHR1	ENST00000623527.4	TSL:1 MANE Select	c.439-208C>A		intron	N/A	ENSP00000485478.1
	CDHR1	ENST00000332904.7	TSL:1	c.439-208C>A		intron	N/A	ENSP00000331063.3

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78562 AN: 151720 Hom.: 21111 Cov.: 31

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.503

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.518 AC: 78675 AN: 151840 Hom.: 21159 Cov.: 31 AF XY: 0.516 AC XY: 38298 AN XY: 74230

African (AFR) AF: 0.680 AC: 28144 AN: 41382

American (AMR) AF: 0.526 AC: 8030 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1640 AN: 3466

East Asian (EAS) AF: 0.390 AC: 1998 AN: 5128

South Asian (SAS) AF: 0.440 AC: 2115 AN: 4808

European-Finnish (FIN) AF: 0.443 AC: 4683 AN: 10564

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30601 AN: 67910

Other (OTH) AF: 0.508 AC: 1072 AN: 2110

Alfa AF: 0.467 Hom.: 20776

Bravo AF: 0.534

Asia WGS AF: 0.471 AC: 1641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.085
DANN	Benign	0.37
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs10788333; hg19: chr10-85960149;