Genetic Variant CDHR5:p.Ala687Thr (chr11-618013-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021924.5(CDHR5):c.2059G>A(p.Ala687Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,610,710 control chromosomes in the GnomAD database, including 39,855 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.

Frequency

Genomes: 𝑓 0.22 ( 3906 hom., cov: 32)

Exomes 𝑓: 0.22 ( 35949 hom. )

Consequence

CDHR5
NM_021924.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.04

Publications

16 publications found

Variant links:

Genes affected

CDHR5 (HGNC:7521): (cadherin related family member 5) This gene is a novel mucin-like gene that is a member of the cadherin superfamily. While encoding nonpolymorphic tandem repeats rich in proline, serine and threonine similar to mucin proteins, the gene also contains sequence encoding calcium-binding motifs found in all cadherins. The role of the hybrid extracellular region and the specific function of this protein have not yet been determined. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jan 2010]

CDHR5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004850924).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDHR5	NM_021924.5 link	c.2059G>A	p.Ala687Thr	missense_variant	Exon 14 of 15	ENST00000397542.7	NP_068743.3	Q9HBB8-1B4DV98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDHR5	ENST00000397542.7 link	c.2059G>A	p.Ala687Thr	missense_variant	Exon 14 of 15	1	NM_021924.5	ENSP00000380676.2		Q9HBB8-1

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33697

AN:

151892

Hom.:

3906

Cov.:

show subpopulations

Gnomad AFR

AF:

0.267

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.0249

Gnomad SAS

AF:

0.0967

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.233

GnomAD2 exomes

AF:

0.196

AC:

48179

AN:

245240

AF XY:

0.189

show subpopulations

Gnomad AFR exome

AF:

0.266

Gnomad AMR exome

AF:

0.281

Gnomad ASJ exome

AF:

0.225

Gnomad EAS exome

AF:

0.0277

Gnomad FIN exome

AF:

0.146

Gnomad NFE exome

AF:

0.221

Gnomad OTH exome

AF:

0.199

GnomAD4 exome

AF:

0.216

AC:

314968

AN:

1458700

Hom.:

35949

Cov.:

AF XY:

0.212

AC XY:

153841

AN XY:

725696

show subpopulations

African (AFR)

AF:

0.268

AC:

8972

AN:

33446

American (AMR)

AF:

0.278

AC:

12358

AN:

44500

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

5821

AN:

26096

East Asian (EAS)

AF:

0.0226

AC:

897

AN:

39684

South Asian (SAS)

AF:

0.107

AC:

9215

AN:

86110

European-Finnish (FIN)

AF:

0.155

AC:

8029

AN:

51934

Middle Eastern (MID)

AF:

0.165

AC:

951

AN:

5768

European-Non Finnish (NFE)

AF:

0.231

AC:

256258

AN:

1110842

Other (OTH)

AF:

0.207

AC:

12467

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

12706

25411

38117

50822

63528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8792

17584

26376

35168

43960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.222

AC:

33717

AN:

152010

Hom.:

3906

Cov.:

AF XY:

0.213

AC XY:

15846

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.267

AC:

11048

AN:

41438

American (AMR)

AF:

0.245

AC:

3753

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

799

AN:

3466

East Asian (EAS)

AF:

0.0250

AC:

129

AN:

5168

South Asian (SAS)

AF:

0.0957

AC:

461

AN:

4816

European-Finnish (FIN)

AF:

0.144

AC:

1521

AN:

10586

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.225

AC:

15304

AN:

67940

Other (OTH)

AF:

0.232

AC:

487

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1320

2641

3961

5282

6602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

336

672

1008

1344

1680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.226

Hom.:

2654

Bravo

AF:

0.232

TwinsUK

AF:

0.225

AC:

834

ALSPAC

AF:

0.238

AC:

916

ESP6500AA

AF:

0.275

AC:

1212

ESP6500EA

AF:

0.242

AC:

2084

ExAC

AF:

0.194

AC:

23436

Asia WGS

AF:

0.0900

AC:

313

AN:

3478

EpiCase

AF:

0.233

EpiControl

AF:

0.228

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.93

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.0088

T;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.51

T;.;T

MetaRNN

Benign

0.0049

T;T;T

MetaSVM

Benign

-0.98

PhyloP100

-1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.65

N;N;N

REVEL

Benign

0.0070

Sift

Benign

0.45

T;T;T

Sift4G

Benign

0.52

T;T;T

Polyphen

0.0050

B;B;B

Vest4

0.11

MPC

0.042

ClinPred

0.00082

GERP RS

-3.3

Varity_R

0.021

gMVP

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over