10-84211677-C-T

Variant names:

• chr10-84211677-C-T
• rs116594644
• NM_033100.4:c.1515C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_033100.4(CDHR1):​c.1515C>T​(p.Gly505Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 1,613,980 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (61 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (73 hom.)
• Consequence: CDHR1 NM_033100.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.943
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 10-84211677-C-T is Benign according to our data. Variant chr10-84211677-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.943 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0504 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.1515C>T	p.Gly505Gly	synonymous	Exon 14 of 17	NP_149091.1
	CDHR1	NM_001171971.3		c.1515C>T	p.Gly505Gly	synonymous	Exon 14 of 17	NP_001165442.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDHR1	ENST00000623527.4	TSL:1 MANE Select	c.1515C>T	p.Gly505Gly	synonymous	Exon 14 of 17	ENSP00000485478.1
	CDHR1	ENST00000332904.7	TSL:1	c.1515C>T	p.Gly505Gly	synonymous	Exon 14 of 17	ENSP00000331063.3
	CDHR1	ENST00000926454.1		c.1464C>T	p.Gly488Gly	synonymous	Exon 13 of 16	ENSP00000596513.1

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2317 AN: 152048 Hom.: 62 Cov.: 33

Gnomad AFR AF: 0.0523

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00577

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00422 AC: 1062 AN: 251480 AF XY: 0.00313

Gnomad AFR exome AF: 0.0547

Gnomad AMR exome AF: 0.00263

Gnomad ASJ exome AF: 0.00258

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000325

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00174 AC: 2549 AN: 1461812 Hom.: 73 Cov.: 31 AF XY: 0.00150 AC XY: 1092 AN XY: 727226

African (AFR) AF: 0.0550 AC: 1838 AN: 33448

American (AMR) AF: 0.00309 AC: 138 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00218 AC: 57 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00745 AC: 43 AN: 5768

European-Non Finnish (NFE) AF: 0.000157 AC: 175 AN: 1111984

Other (OTH) AF: 0.00457 AC: 276 AN: 60380

GnomAD4 genome AF: 0.0153 AC: 2322 AN: 152168 Hom.: 61 Cov.: 33 AF XY: 0.0140 AC XY: 1044 AN XY: 74402

African (AFR) AF: 0.0522 AC: 2167 AN: 41494

American (AMR) AF: 0.00576 AC: 88 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68006

Other (OTH) AF: 0.0109 AC: 23 AN: 2112

Alfa AF: 0.00602 Hom.: 9

Bravo AF: 0.0167

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000593

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Cone-Rod Dystrophy, Recessive (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.8
DANN	Benign	0.59
PhyloP100		-0.94
Mutation Taster		=99/1	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: rs116594644; hg19: chr10-85971433;