Variant chr11-618998-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000397542.7(CDHR5):c.1561C>T(p.Pro521Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,612,530 control chromosomes in the GnomAD database, including 242,696 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 0.48 ( 18940 hom., cov: 29)

Exomes 𝑓: 0.55 ( 223756 hom. )

Consequence

CDHR5
ENST00000397542.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.307

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.9095008E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDHR5	NM_021924.5 linkuse as main transcript	c.1561C>T	p.Pro521Ser	missense_variant	13/15	ENST00000397542.7	NP_068743.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDHR5	ENST00000397542.7 linkuse as main transcript	c.1561C>T	p.Pro521Ser	missense_variant	13/15	1	NM_021924.5	ENSP00000380676	P2	Q9HBB8-1

Frequencies

GnomAD3 genomes

AF:

0.484

AC:

73107

AN:

150950

Hom.:

18946

Cov.:

show subpopulations

Gnomad AFR

AF:

0.290

Gnomad AMI

AF:

0.657

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.528

Gnomad EAS

AF:

0.696

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.666

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.555

Gnomad OTH

AF:

0.491

GnomAD3 exomes

AF:

0.542

AC:

135495

AN:

250138

Hom.:

38082

AF XY:

0.551

AC XY:

74736

AN XY:

135518

show subpopulations

Gnomad AFR exome

AF:

0.286

Gnomad AMR exome

AF:

0.416

Gnomad ASJ exome

AF:

0.539

Gnomad EAS exome

AF:

0.690

Gnomad SAS exome

AF:

0.578

Gnomad FIN exome

AF:

0.651

Gnomad NFE exome

AF:

0.561

Gnomad OTH exome

AF:

0.554

GnomAD4 exome

AF:

0.550

AC:

803258

AN:

1461466

Hom.:

223756

Cov.:

AF XY:

0.552

AC XY:

401240

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.281

Gnomad4 AMR exome

AF:

0.421

Gnomad4 ASJ exome

AF:

0.539

Gnomad4 EAS exome

AF:

0.731

Gnomad4 SAS exome

AF:

0.575

Gnomad4 FIN exome

AF:

0.637

Gnomad4 NFE exome

AF:

0.551

Gnomad4 OTH exome

AF:

0.540

GnomAD4 genome

AF:

0.484

AC:

73111

AN:

151064

Hom.:

18940

Cov.:

AF XY:

0.491

AC XY:

36239

AN XY:

73764

show subpopulations

Gnomad4 AFR

AF:

0.290

Gnomad4 AMR

AF:

0.446

Gnomad4 ASJ

AF:

0.528

Gnomad4 EAS

AF:

0.695

Gnomad4 SAS

AF:

0.589

Gnomad4 FIN

AF:

0.666

Gnomad4 NFE

AF:

0.555

Gnomad4 OTH

AF:

0.490

Alfa

AF:

0.488

Hom.:

7381

Bravo

AF:

0.461

TwinsUK

AF:

0.543

AC:

2015

ALSPAC

AF:

0.548

AC:

2113

ESP6500AA

AF:

0.288

AC:

1270

ESP6500EA

AF:

0.538

AC:

4629

ExAC

AF:

0.543

AC:

65915

Asia WGS

AF:

0.577

AC:

2008

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.1

DANN

Benign

0.65

DEOGEN2

Benign

0.0053

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.34

T;.

MetaRNN

Benign

0.0000029

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.27

N;N

REVEL

Benign

0.0090

Sift

Benign

0.41

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.093

B;B

Vest4

0.19

MPC

0.057

ClinPred

0.0056

GERP RS

1.6

Varity_R

0.021

gMVP

0.29

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over