rs3814213

Variant names:

• chr10-84214480-T-C
• rs3814213
• NM_033100.4:c.2439T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-84214480-T-C
• chr10-84214480-T-A
• chr10-84214480-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033100.4(CDHR1):​c.2439T>C​(p.Thr813Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 1,608,950 control chromosomes in the GnomAD database, including 228,762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (27627 hom., cov: 33)
  • Exomes 𝑓: 0.52 (201135 hom.)
• Consequence: CDHR1 NM_033100.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -6.31
• Publications: 28 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 10-84214480-T-C is Benign according to our data. Variant chr10-84214480-T-C is described in ClinVar as Benign. ClinVar VariationId is 194794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 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.2439T>C	p.Thr813Thr	synonymous	Exon 17 of 17	NP_149091.1	Q96JP9-1
	CDHR1	NM_001171971.3		c.2040+1132T>C		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.2439T>C	p.Thr813Thr	synonymous	Exon 17 of 17	ENSP00000485478.1	Q96JP9-1
	CDHR1	ENST00000332904.7	TSL:1	c.2040+1132T>C		intron	N/A	ENSP00000331063.3	Q96JP9-2
	CDHR1	ENST00000926454.1		c.2388T>C	p.Thr796Thr	synonymous	Exon 16 of 16	ENSP00000596513.1

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89508 AN: 151920 Hom.: 27574 Cov.: 33

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.568

GnomAD2 exomes AF: 0.532 AC: 131434 AN: 246990 AF XY: 0.524

Gnomad AFR exome AF: 0.784

Gnomad AMR exome AF: 0.594

Gnomad ASJ exome AF: 0.565

Gnomad EAS exome AF: 0.393

Gnomad FIN exome AF: 0.476

Gnomad NFE exome AF: 0.524

Gnomad OTH exome AF: 0.517

GnomAD4 exome AF: 0.522 AC: 761089 AN: 1456910 Hom.: 201135 Cov.: 64 AF XY: 0.520 AC XY: 376714 AN XY: 725010

African (AFR) AF: 0.794 AC: 26544 AN: 33450

American (AMR) AF: 0.593 AC: 26507 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 14864 AN: 26108

East Asian (EAS) AF: 0.355 AC: 14074 AN: 39692

South Asian (SAS) AF: 0.469 AC: 40445 AN: 86254

European-Finnish (FIN) AF: 0.480 AC: 23467 AN: 48850

Middle Eastern (MID) AF: 0.501 AC: 2890 AN: 5766

European-Non Finnish (NFE) AF: 0.522 AC: 580039 AN: 1111756

Other (OTH) AF: 0.535 AC: 32259 AN: 60340

GnomAD4 genome AF: 0.589 AC: 89624 AN: 152040 Hom.: 27627 Cov.: 33 AF XY: 0.584 AC XY: 43421 AN XY: 74306

African (AFR) AF: 0.782 AC: 32428 AN: 41492

American (AMR) AF: 0.583 AC: 8907 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1983 AN: 3472

East Asian (EAS) AF: 0.402 AC: 2069 AN: 5142

South Asian (SAS) AF: 0.477 AC: 2295 AN: 4814

European-Finnish (FIN) AF: 0.468 AC: 4952 AN: 10570

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35327 AN: 67952

Other (OTH) AF: 0.572 AC: 1209 AN: 2114

Alfa AF: 0.543 Hom.: 29146

Bravo AF: 0.608

Asia WGS AF: 0.496 AC: 1726 AN: 3478

EpiCase AF: 0.517

EpiControl AF: 0.524

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	1	Cone-rod dystrophy 15 (1)
-	-	1	Cone-Rod Dystrophy, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.066
DANN	Benign	0.45
PhyloP100		-6.3
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: rs3814213; hg19: chr10-85974236; COSMIC: COSV60562725; COSMIC: COSV60562725;