chr10-84214625-A-G

Variant names:

• chr10-84214625-A-G
• rs3814212
• NM_033100.4:c.*4A>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.*4A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 1,599,184 control chromosomes in the GnomAD database, including 282,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (34611 hom., cov: 31)
  • Exomes 𝑓: 0.58 (248062 hom.)
• Consequence: CDHR1 NM_033100.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.160
• Publications: 19 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-84214625-A-G is Benign according to our data. Variant chr10-84214625-A-G is described in ClinVar as Benign. ClinVar VariationId is 194795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 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.*4A>G		3_prime_UTR	Exon 17 of 17	NP_149091.1
	CDHR1	NM_001171971.3		c.2040+1277A>G		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.*4A>G		3_prime_UTR	Exon 17 of 17	ENSP00000485478.1
	CDHR1	ENST00000332904.7	TSL:1	c.2040+1277A>G		intron	N/A	ENSP00000331063.3
	CDHR1	ENST00000459673.1	TSL:2	n.1016A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100153 AN: 151878 Hom.: 34548 Cov.: 31

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.633

GnomAD2 exomes AF: 0.586 AC: 139883 AN: 238670 AF XY: 0.576

Gnomad AFR exome AF: 0.881

Gnomad AMR exome AF: 0.636

Gnomad ASJ exome AF: 0.655

Gnomad EAS exome AF: 0.393

Gnomad FIN exome AF: 0.552

Gnomad NFE exome AF: 0.586

Gnomad OTH exome AF: 0.590

GnomAD4 exome AF: 0.581 AC: 841118 AN: 1447188 Hom.: 248062 Cov.: 51 AF XY: 0.577 AC XY: 415643 AN XY: 720308

African (AFR) AF: 0.886 AC: 29674 AN: 33474

American (AMR) AF: 0.637 AC: 28479 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 17283 AN: 26128

East Asian (EAS) AF: 0.355 AC: 14103 AN: 39696

South Asian (SAS) AF: 0.485 AC: 41817 AN: 86232

European-Finnish (FIN) AF: 0.556 AC: 21762 AN: 39156

Middle Eastern (MID) AF: 0.583 AC: 3361 AN: 5766

European-Non Finnish (NFE) AF: 0.583 AC: 648483 AN: 1111736

Other (OTH) AF: 0.600 AC: 36156 AN: 60300

GnomAD4 genome AF: 0.660 AC: 100278 AN: 151996 Hom.: 34611 Cov.: 31 AF XY: 0.654 AC XY: 48598 AN XY: 74298

African (AFR) AF: 0.877 AC: 36396 AN: 41480

American (AMR) AF: 0.644 AC: 9847 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2323 AN: 3472

East Asian (EAS) AF: 0.403 AC: 2061 AN: 5120

South Asian (SAS) AF: 0.495 AC: 2379 AN: 4808

European-Finnish (FIN) AF: 0.553 AC: 5843 AN: 10562

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39554 AN: 67958

Other (OTH) AF: 0.636 AC: 1341 AN: 2108

Alfa AF: 0.618 Hom.: 40174

Bravo AF: 0.678

Asia WGS AF: 0.513 AC: 1786 AN: 3478

EpiCase AF: 0.580

EpiControl AF: 0.585

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Nov 19, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Apr 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Cone-Rod Dystrophy, Recessive Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.7
DANN	Benign	0.38
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3814212; hg19: chr10-85974381; COSMIC: COSV60562734; COSMIC: COSV60562734;