rs4244946

chr10-84213509-G-Achr10-84213509-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033100.4(CDHR1):c.2040+161G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,102 control chromosomes in the GnomAD database, including 15,297 homozygotes. 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: 𝑓 0.42 (15297 hom., cov: 33)
• Consequence: CDHR1 NM_033100.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDHR1	NM_033100.4	c.2040+161G>A		intron_variant		ENST00000623527.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDHR1	ENST00000623527.4	c.2040+161G>A		intron_variant		1	NM_033100.4	P2

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63187 AN: 151984 Hom.: 15264 Cov.: 33

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.375

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.416 AC: 63280 AN: 152102 Hom.: 15297 Cov.: 33 AF XY: 0.417 AC XY: 31003 AN XY: 74368

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.376

Alfa AF: 0.302 Hom.: 3666

Bravo AF: 0.432

Asia WGS AF: 0.340 AC: 1184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.43
Dann	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs4244946; hg19: chr10-85973265;