NM_033100.4:c.-64G>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033100.4(CDHR1):​c.-64G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000082 in 1,219,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: CDHR1 NM_033100.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.677
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.20e-7 AC: 1 AN: 1219798 Hom.: 0 Cov.: 18 AF XY: 0.00000166 AC XY: 1 AN XY: 602318

African (AFR) AF: 0.00 AC: 0 AN: 23694

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 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: 0.00000102 AC: 1 AN: 980220

Other (OTH) AF: 0.00 AC: 0 AN: 51002

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.83
PhyloP100		0.68
PromoterAI		0.010	Neutral

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;