rs4244946

Variant names:

• chr10-84213509-G-A
• rs4244946
• NM_033100.4:c.2040+161G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-84213509-G-A
• chr10-84213509-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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 -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.

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.2040+161G>A		intron	N/A	NP_149091.1	Q96JP9-1
	CDHR1	NM_001171971.3		c.2040+161G>A		intron	N/A	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.2040+161G>A		intron	N/A	ENSP00000485478.1	Q96JP9-1
	CDHR1	ENST00000332904.7	TSL:1	c.2040+161G>A		intron	N/A	ENSP00000331063.3	Q96JP9-2
	CDHR1	ENST00000926454.1		c.1989+161G>A		intron	N/A	ENSP00000596513.1

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

African (AFR) AF: 0.681 AC: 28229 AN: 41474

American (AMR) AF: 0.394 AC: 6019 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1243 AN: 3470

East Asian (EAS) AF: 0.262 AC: 1357 AN: 5170

South Asian (SAS) AF: 0.341 AC: 1642 AN: 4818

European-Finnish (FIN) AF: 0.369 AC: 3908 AN: 10588

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19871 AN: 67970

Other (OTH) AF: 0.376 AC: 794 AN: 2114

Alfa AF: 0.306 Hom.: 4256

Bravo AF: 0.432

Asia WGS AF: 0.340 AC: 1184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.43
DANN	Benign	0.50
PhyloP100		-0.27
PromoterAI		0.0056	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4244946;

hg19: chr10-85973265;

COSMIC: COSV107411983;

COSMIC: COSV107411983;