rs10270308

Variant names:

• chr7-106030821-T-C
• rs10270308
• NM_152750.5:c.2334T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000317716.14(CDHR3):​c.2334T>C​(p.Asp778Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,610,650 control chromosomes in the GnomAD database, including 8,048 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 0.12 (2747 hom., cov: 33)
  • Exomes 𝑓: 0.031 (5301 hom.)
• Consequence: CDHR3 ENST00000317716.14 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529
• Publications: 14 publications found

Genes affected

CDHR3 (HGNC:26308): (cadherin related family member 3) Predicted to enable cadherin binding activity and calcium ion binding activity. Predicted to be involved in calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules; cell morphogenesis; and cell-cell junction organization. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.529 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000317716.14. 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
	CDHR3	NM_152750.5	MANE Select	c.2334T>C	p.Asp778Asp	synonymous	Exon 18 of 19	NP_689963.2
	CDHR3	NM_001301161.2		c.2070T>C	p.Asp690Asp	synonymous	Exon 17 of 18	NP_001288090.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDHR3	ENST00000317716.14	TSL:1 MANE Select	c.2334T>C	p.Asp778Asp	synonymous	Exon 18 of 19	ENSP00000325954.9
	CDHR3	ENST00000478080.5	TSL:2	c.2070T>C	p.Asp690Asp	synonymous	Exon 17 of 18	ENSP00000417771.1
	CDHR3	ENST00000468143.1	TSL:4	n.185T>C		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18282 AN: 152124 Hom.: 2738 Cov.: 33

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.0727

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.00570

Gnomad OTH AF: 0.110

GnomAD2 exomes AF: 0.0770 AC: 18760 AN: 243556 AF XY: 0.0667

Gnomad AFR exome AF: 0.330

Gnomad AMR exome AF: 0.129

Gnomad ASJ exome AF: 0.00151

Gnomad EAS exome AF: 0.371

Gnomad FIN exome AF: 0.0273

Gnomad NFE exome AF: 0.00601

Gnomad OTH exome AF: 0.0464

GnomAD4 exome AF: 0.0312 AC: 45455 AN: 1458406 Hom.: 5301 Cov.: 30 AF XY: 0.0303 AC XY: 21936 AN XY: 725106

African (AFR) AF: 0.340 AC: 11348 AN: 33364

American (AMR) AF: 0.128 AC: 5639 AN: 44208

Ashkenazi Jewish (ASJ) AF: 0.00119 AC: 31 AN: 26034

East Asian (EAS) AF: 0.352 AC: 13911 AN: 39532

South Asian (SAS) AF: 0.0515 AC: 4388 AN: 85266

European-Finnish (FIN) AF: 0.0258 AC: 1375 AN: 53236

Middle Eastern (MID) AF: 0.0321 AC: 185 AN: 5762

European-Non Finnish (NFE) AF: 0.00455 AC: 5054 AN: 1110768

Other (OTH) AF: 0.0585 AC: 3524 AN: 60236

GnomAD4 genome AF: 0.120 AC: 18330 AN: 152244 Hom.: 2747 Cov.: 33 AF XY: 0.120 AC XY: 8943 AN XY: 74442

African (AFR) AF: 0.326 AC: 13508 AN: 41496

American (AMR) AF: 0.101 AC: 1551 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.380 AC: 1970 AN: 5186

South Asian (SAS) AF: 0.0724 AC: 349 AN: 4822

European-Finnish (FIN) AF: 0.0271 AC: 288 AN: 10616

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00570 AC: 388 AN: 68026

Other (OTH) AF: 0.111 AC: 235 AN: 2112

Alfa AF: 0.0480 Hom.: 4352

Bravo AF: 0.137

Asia WGS AF: 0.226 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.2
DANN	Benign	0.59
PhyloP100		0.53
Mutation Taster		=91/9	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: rs10270308; hg19: chr7-105671267; COSMIC: COSV58421940; COSMIC: COSV58421940;