rs10270308

chr7-106030821-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_152750.5(CDHR3):c.2334T>C(p.Asp778=) 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 NM_152750.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDHR3	NM_152750.5	c.2334T>C	p.Asp778=	synonymous_variant	18/19	ENST00000317716.14
CDHR3	NM_001301161.2	c.2070T>C	p.Asp690=	synonymous_variant	17/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDHR3	ENST00000317716.14	c.2334T>C	p.Asp778=	synonymous_variant	18/19	1	NM_152750.5	P1

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

GnomAD3 exomes AF: 0.0770 AC: 18760 AN: 243556 Hom.: 2342 AF XY: 0.0667 AC XY: 8809 AN XY: 132062

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 SAS exome AF: 0.0525

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

Gnomad4 AFR exome AF: 0.340

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.352

Gnomad4 SAS exome AF: 0.0515

Gnomad4 FIN exome AF: 0.0258

Gnomad4 NFE exome AF: 0.00455

Gnomad4 OTH exome AF: 0.0585

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

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.0724

Gnomad4 FIN AF: 0.0271

Gnomad4 NFE AF: 0.00570

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0332 Hom.: 1453

Bravo AF: 0.137

Asia WGS AF: 0.226 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	7.2
Dann	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs10270308; hg19: chr7-105671267; COSMIC: COSV58421940; COSMIC: COSV58421940;