rs4933975

Variant names:

• chr10-84200639-A-G
• rs4933975
• NM_033100.4:c.477A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-84200639-A-G
• chr10-84200639-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_033100.4(CDHR1):​c.477A>G​(p.Ala159Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 1,609,788 control chromosomes in the GnomAD database, including 178,669 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21428 hom., cov: 32)
  • Exomes 𝑓: 0.46 (157241 hom.)
• Consequence: CDHR1 NM_033100.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -2.03
• Publications: 22 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 10-84200639-A-G is Benign according to our data. Variant chr10-84200639-A-G is described in ClinVar as Benign. ClinVar VariationId is 262215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDHR1	NM_033100.4	MANE Select	c.477A>G	p.Ala159Ala	synonymous	Exon 6 of 17	NP_149091.1
	CDHR1	NM_001171971.3		c.477A>G	p.Ala159Ala	synonymous	Exon 6 of 17	NP_001165442.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDHR1	ENST00000623527.4	TSL:1 MANE Select	c.477A>G	p.Ala159Ala	synonymous	Exon 6 of 17	ENSP00000485478.1
	CDHR1	ENST00000332904.7	TSL:1	c.477A>G	p.Ala159Ala	synonymous	Exon 6 of 17	ENSP00000331063.3

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79046 AN: 151964 Hom.: 21379 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.503

GnomAD2 exomes AF: 0.474 AC: 116518 AN: 245878 AF XY: 0.466

Gnomad AFR exome AF: 0.688

Gnomad AMR exome AF: 0.556

Gnomad ASJ exome AF: 0.456

Gnomad EAS exome AF: 0.380

Gnomad FIN exome AF: 0.445

Gnomad NFE exome AF: 0.453

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.462 AC: 672914 AN: 1457706 Hom.: 157241 Cov.: 38 AF XY: 0.459 AC XY: 332768 AN XY: 724874

African (AFR) AF: 0.693 AC: 23163 AN: 33432

American (AMR) AF: 0.554 AC: 24535 AN: 44314

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 12095 AN: 26036

East Asian (EAS) AF: 0.346 AC: 13721 AN: 39658

South Asian (SAS) AF: 0.437 AC: 37379 AN: 85550

European-Finnish (FIN) AF: 0.450 AC: 23985 AN: 53286

Middle Eastern (MID) AF: 0.413 AC: 2377 AN: 5758

European-Non Finnish (NFE) AF: 0.457 AC: 507379 AN: 1109398

Other (OTH) AF: 0.469 AC: 28280 AN: 60274

GnomAD4 genome AF: 0.521 AC: 79159 AN: 152082 Hom.: 21428 Cov.: 32 AF XY: 0.518 AC XY: 38490 AN XY: 74340

African (AFR) AF: 0.687 AC: 28517 AN: 41502

American (AMR) AF: 0.528 AC: 8068 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1642 AN: 3468

East Asian (EAS) AF: 0.389 AC: 2010 AN: 5168

South Asian (SAS) AF: 0.440 AC: 2121 AN: 4824

European-Finnish (FIN) AF: 0.442 AC: 4672 AN: 10560

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30661 AN: 67958

Other (OTH) AF: 0.508 AC: 1072 AN: 2110

Alfa AF: 0.477 Hom.: 27403

Bravo AF: 0.537

Asia WGS AF: 0.471 AC: 1640 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Cone-rod dystrophy 15 (1)
-	-	1	Cone-Rod Dystrophy, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.016
DANN	Benign	0.29
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs4933975; hg19: chr10-85960395; COSMIC: COSV60561610; COSMIC: COSV60561610;