rs79239487

Variant names:

• chr10-84196656-G-A
• rs79239487
• NM_033100.4:c.297+6G>A

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.297+6G>A variant causes a splice 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. 3/3 splice prediction tools predict no significant impact on normal splicing. 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_region, intron
• Scores: Splicing: ADA: 0.0005256
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0330
• Publications: 1 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=-0.75).
• BP6: Variant 10-84196656-G-A is Benign according to our data. Variant chr10-84196656-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
CDHR1	NM_033100.4	c.297+6G>A		splice_region_variant, intron_variant	Intron 3 of 16	ENST00000623527.4	NP_149091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDHR1	ENST00000623527.4	c.297+6G>A		splice_region_variant, intron_variant	Intron 3 of 16	1	NM_033100.4	ENSP00000485478.1
CDHR1	ENST00000332904.7	c.297+6G>A		splice_region_variant, intron_variant	Intron 3 of 16	1		ENSP00000331063.3

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

GnomAD2 exomes AF: 0.0148 AC: 3733 AN: 251482 AF XY: 0.0154

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 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

African (AFR) AF: 0.0145 AC: 487 AN: 33480

American (AMR) AF: 0.000604 AC: 27 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26134

East Asian (EAS) AF: 0.109 AC: 4343 AN: 39700

South Asian (SAS) AF: 0.0336 AC: 2899 AN: 86258

European-Finnish (FIN) AF: 0.00528 AC: 282 AN: 53414

Middle Eastern (MID) AF: 0.00381 AC: 22 AN: 5768

European-Non Finnish (NFE) AF: 0.000490 AC: 545 AN: 1111998

Other (OTH) AF: 0.00997 AC: 602 AN: 60394

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

African (AFR) AF: 0.0134 AC: 558 AN: 41570

American (AMR) AF: 0.00157 AC: 24 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.125 AC: 646 AN: 5178

South Asian (SAS) AF: 0.0367 AC: 177 AN: 4820

European-Finnish (FIN) AF: 0.00461 AC: 49 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68020

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00240 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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cone-Rod Dystrophy, Recessive Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.3
DANN	Benign	0.61
PhyloP100		-0.033
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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