rs114273269

Variant names:

• chr10-84194760-C-T
• rs114273269
• NM_033100.4:c.-1C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_033100.4(CDHR1):​c.-1C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,519,356 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0062 (12 hom., cov: 33)
  • Exomes 𝑓: 0.00062 (11 hom.)
• Consequence: CDHR1 NM_033100.4 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.416
• 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 10-84194760-C-T is Benign according to our data. Variant chr10-84194760-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 193475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0062 (944/152294) while in subpopulation AFR AF = 0.022 (915/41582). AF 95% confidence interval is 0.0208. There are 12 homozygotes in GnomAd4. There are 423 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR,AD gene

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.-1C>T		5_prime_UTR	Exon 1 of 17	NP_149091.1	Q96JP9-1
	CDHR1	NM_001171971.3		c.-1C>T		5_prime_UTR	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.-1C>T		5_prime_UTR	Exon 1 of 17	ENSP00000485478.1	Q96JP9-1
	CDHR1	ENST00000332904.7	TSL:1	c.-1C>T		5_prime_UTR	Exon 1 of 17	ENSP00000331063.3	Q96JP9-2
	CDHR1	ENST00000926454.1		c.-1C>T		5_prime_UTR	Exon 1 of 16	ENSP00000596513.1

Frequencies

GnomAD3 genomes AF: 0.00620 AC: 944 AN: 152184 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.000909 AC: 106 AN: 116578 AF XY: 0.000653

Gnomad AFR exome AF: 0.0247

Gnomad AMR exome AF: 0.000431

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000232

Gnomad OTH exome AF: 0.000556

GnomAD4 exome AF: 0.000617 AC: 843 AN: 1367062 Hom.: 11 Cov.: 31 AF XY: 0.000494 AC XY: 333 AN XY: 674318

African (AFR) AF: 0.0254 AC: 743 AN: 29280

American (AMR) AF: 0.000665 AC: 23 AN: 34598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24496

East Asian (EAS) AF: 0.00 AC: 0 AN: 34196

South Asian (SAS) AF: 0.0000385 AC: 3 AN: 77964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33382

Middle Eastern (MID) AF: 0.000250 AC: 1 AN: 4006

European-Non Finnish (NFE) AF: 0.00000373 AC: 4 AN: 1072188

Other (OTH) AF: 0.00121 AC: 69 AN: 56952

GnomAD4 genome AF: 0.00620 AC: 944 AN: 152294 Hom.: 12 Cov.: 33 AF XY: 0.00568 AC XY: 423 AN XY: 74472

African (AFR) AF: 0.0220 AC: 915 AN: 41582

American (AMR) AF: 0.000915 AC: 14 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00381 Hom.: 0

Bravo AF: 0.00672

Asia WGS AF: 0.00145 AC: 5 AN: 3472

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cone-rod dystrophy 15 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.88
PhyloP100		0.42
PromoterAI		-0.12	Neutral
Mutation Taster		=299/1	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: rs114273269; hg19: chr10-85954516;