rs6967330

chr7-106018005-G-A

Variant summary

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

The NM_152750.5(CDHR3):c.1586G>A(p.Cys529Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,611,648 control chromosomes in the GnomAD database, including 27,565 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.20 (3386 hom., cov: 31)
  • Exomes 𝑓: 0.18 (24179 hom.)
• Consequence: CDHR3 NM_152750.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0056328475).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDHR3	NM_152750.5	c.1586G>A	p.Cys529Tyr	missense_variant	12/19	ENST00000317716.14
CDHR3	NM_001301161.2	c.1322G>A	p.Cys441Tyr	missense_variant	11/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDHR3	ENST00000317716.14	c.1586G>A	p.Cys529Tyr	missense_variant	12/19	1	NM_152750.5	P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30769 AN: 151900 Hom.: 3378 Cov.: 31

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0718

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.210

GnomAD3 exomes AF: 0.185 AC: 46124 AN: 248940 Hom.: 4761 AF XY: 0.189 AC XY: 25473 AN XY: 135062

Gnomad AFR exome AF: 0.262

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.0704

Gnomad SAS exome AF: 0.224

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.187

GnomAD4 exome AF: 0.176 AC: 257227 AN: 1459630 Hom.: 24179 Cov.: 33 AF XY: 0.179 AC XY: 129630 AN XY: 726206

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.0814

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.283

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.203 AC: 30826 AN: 152018 Hom.: 3386 Cov.: 31 AF XY: 0.207 AC XY: 15406 AN XY: 74298

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.0720

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.217

Alfa AF: 0.174 Hom.: 4867

Bravo AF: 0.198

TwinsUK AF: 0.170 AC: 630

ALSPAC AF: 0.165 AC: 636

ESP6500AA AF: 0.249 AC: 967

ESP6500EA AF: 0.169 AC: 1405

ExAC AF: 0.189 AC: 22787

Asia WGS AF: 0.197 AC: 686 AN: 3478

EpiCase AF: 0.177

EpiControl AF: 0.178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	8.7
Dann	Benign	0.49
DEOGEN2	Benign	0.0030	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.20	T;T
MetaRNN	Benign	0.0056	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.4	N;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	4.5	N;N
REVEL	Benign	0.14
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.029
MPC		0.048
ClinPred		0.0026	T
GERP RS		4.4
Varity_R		0.056
gMVP		0.28

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: rs6967330; hg19: chr7-105658451;