NM_033100.4:c.964-994A>G

Variant names:

• chr10-84207180-A-G
• rs7089142
• NM_033100.4:c.964-994A>G

Variant summary

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

The NM_033100.4(CDHR1):​c.964-994A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,856 control chromosomes in the GnomAD database, including 23,326 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 0.54 (23326 hom., cov: 30)
• Consequence: CDHR1 NM_033100.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDHR1	NM_033100.4	MANE Select	c.964-994A>G		intron	N/A	NP_149091.1	Q96JP9-1
	CDHR1	NM_001171971.3		c.964-994A>G		intron	N/A	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.964-994A>G		intron	N/A	ENSP00000485478.1	Q96JP9-1
	CDHR1	ENST00000332904.7	TSL:1	c.964-994A>G		intron	N/A	ENSP00000331063.3	Q96JP9-2
	CDHR1	ENST00000926454.1		c.913-994A>G		intron	N/A	ENSP00000596513.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81601 AN: 151738 Hom.: 23277 Cov.: 30

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.538 AC: 81719 AN: 151856 Hom.: 23326 Cov.: 30 AF XY: 0.532 AC XY: 39460 AN XY: 74220

African (AFR) AF: 0.739 AC: 30591 AN: 41370

American (AMR) AF: 0.505 AC: 7703 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1680 AN: 3468

East Asian (EAS) AF: 0.258 AC: 1331 AN: 5162

South Asian (SAS) AF: 0.387 AC: 1858 AN: 4802

European-Finnish (FIN) AF: 0.440 AC: 4635 AN: 10546

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32431 AN: 67928

Other (OTH) AF: 0.520 AC: 1099 AN: 2114

Alfa AF: 0.492 Hom.: 12287

Bravo AF: 0.554

Asia WGS AF: 0.396 AC: 1379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.025
DANN	Benign	0.38
PhyloP100		-2.3
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: rs7089142; hg19: chr10-85966936;