rs79239487

chr10-84196656-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033100.4(CDHR1):c.297+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00664 in 1,614,182 control chromosomes in the GnomAD database, including 401 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0099 (46 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (355 hom.)
• Consequence: CDHR1 NM_033100.4 splice_donor_region, intron
• Scores: Splicing: ADA: 0.0005256
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0330

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 10-84196656-G-A is Benign according to our data. Variant chr10-84196656-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDHR1	NM_033100.4	c.297+6G>A		splice_donor_region_variant, intron_variant		ENST00000623527.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDHR1	ENST00000623527.4	c.297+6G>A		splice_donor_region_variant, intron_variant		1	NM_033100.4	P2
CDHR1	ENST00000332904.7	c.297+6G>A		splice_donor_region_variant, intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.00995 AC: 1514 AN: 152194 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0369

Gnomad FIN AF: 0.00461

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.00956

GnomAD3 exomes AF: 0.0148 AC: 3733 AN: 251482 Hom.: 163 AF XY: 0.0154 AC XY: 2090 AN XY: 135918

Gnomad AFR exome AF: 0.0137

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.123

Gnomad SAS exome AF: 0.0326

Gnomad FIN exome AF: 0.00573

Gnomad NFE exome AF: 0.000659

Gnomad OTH exome AF: 0.00619

GnomAD4 exome AF: 0.00630 AC: 9210 AN: 1461870 Hom.: 355 Cov.: 32 AF XY: 0.00721 AC XY: 5245 AN XY: 727244

Gnomad4 AFR exome AF: 0.0145

Gnomad4 AMR exome AF: 0.000604

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.0336

Gnomad4 FIN exome AF: 0.00528

Gnomad4 NFE exome AF: 0.000490

Gnomad4 OTH exome AF: 0.00997

GnomAD4 genome AF: 0.00994 AC: 1514 AN: 152312 Hom.: 46 Cov.: 32 AF XY: 0.0112 AC XY: 835 AN XY: 74488

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.0367

Gnomad4 FIN AF: 0.00461

Gnomad4 NFE AF: 0.000559

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.00229 Hom.: 2

Bravo AF: 0.0104

Asia WGS AF: 0.0680 AC: 235 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Cone-Rod Dystrophy, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	5.3
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00053
dbscSNV1_RF	Benign	0.042
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

Publications

LitVar

Other links and lift over

dbSNP: rs79239487; hg19: chr10-85956412; COSMIC: COSV60559637;