rs531194884

Variant names:

• chr10-84194697-G-A
• rs531194884
• NM_033100.4:c.-64G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-84194697-G-A
• chr10-84194697-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_033100.4(CDHR1):​c.-64G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,372,022 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0062 (12 hom., cov: 33)
  • Exomes 𝑓: 0.00056 (8 hom.)
• Consequence: CDHR1 NM_033100.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.677
• 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: 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=-0.49).
• BP6: Variant 10-84194697-G-A is Benign according to our data. Variant chr10-84194697-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 301206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00619 (943/152246) while in subpopulation AFR AF = 0.022 (914/41550). AF 95% confidence interval is 0.0208. There are 12 homozygotes in GnomAd4. There are 424 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR,AD gene

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.-64G>A		5_prime_UTR	Exon 1 of 17	NP_149091.1	Q96JP9-1
	CDHR1	NM_001171971.3		c.-64G>A		5_prime_UTR	Exon 1 of 17	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.-64G>A		5_prime_UTR	Exon 1 of 17	ENSP00000485478.1	Q96JP9-1
	CDHR1	ENST00000332904.7	TSL:1	c.-64G>A		5_prime_UTR	Exon 1 of 17	ENSP00000331063.3	Q96JP9-2
	CDHR1	ENST00000926454.1		c.-64G>A		5_prime_UTR	Exon 1 of 16	ENSP00000596513.1

Frequencies

GnomAD3 genomes AF: 0.00620 AC: 943 AN: 152138 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.000559 AC: 682 AN: 1219776 Hom.: 8 Cov.: 18 AF XY: 0.000462 AC XY: 278 AN XY: 602310

African (AFR) AF: 0.0253 AC: 599 AN: 23678

American (AMR) AF: 0.000819 AC: 16 AN: 19542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18536

East Asian (EAS) AF: 0.00 AC: 0 AN: 30528

South Asian (SAS) AF: 0.0000649 AC: 4 AN: 61636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3534

European-Non Finnish (NFE) AF: 0.00000510 AC: 5 AN: 980218

Other (OTH) AF: 0.00114 AC: 58 AN: 50998

GnomAD4 genome AF: 0.00619 AC: 943 AN: 152246 Hom.: 12 Cov.: 33 AF XY: 0.00570 AC XY: 424 AN XY: 74432

African (AFR) AF: 0.0220 AC: 914 AN: 41550

American (AMR) AF: 0.000915 AC: 14 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68004

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00444 Hom.: 0

Bravo AF: 0.00672

Asia WGS AF: 0.00145 AC: 5 AN: 3468

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cone-rod dystrophy 15 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.93
PhyloP100		0.68
PromoterAI		0.018	Neutral
Mutation Taster		=300/0	polymorphism

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: rs531194884; hg19: chr10-85954453;