Variant 11-617967-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_021924.5(CDHR5):c.2105G>C(p.Cys702Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,611,674 control chromosomes in the GnomAD database, including 800,014 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 0.98 ( 73235 hom., cov: 29)

Exomes 𝑓: 1.0 ( 726779 hom. )

Consequence

CDHR5
NM_021924.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.768

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=6.6029924E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.2105G>C	p.Cys702Ser	missense_variant	14/15	ENST00000397542.7	NP_068743.3	Q9HBB8-1B4DV98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDHR5	ENST00000397542.7 linkuse as main transcript	c.2105G>C	p.Cys702Ser	missense_variant	14/15	1	NM_021924.5	ENSP00000380676.2		Q9HBB8-1

Frequencies

GnomAD3 genomes

AF:

0.981

AC:

149070

AN:

151928

Hom.:

73186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.934

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.994

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.988

GnomAD3 exomes

AF:

0.995

AC:

242544

AN:

243750

Hom.:

120703

AF XY:

0.996

AC XY:

132022

AN XY:

132496

show subpopulations

Gnomad AFR exome

AF:

0.932

Gnomad AMR exome

AF:

0.997

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.997

GnomAD4 exome

AF:

0.998

AC:

1456489

AN:

1459628

Hom.:

726779

Cov.:

AF XY:

0.998

AC XY:

724606

AN XY:

725970

show subpopulations

Gnomad4 AFR exome

AF:

0.925

Gnomad4 AMR exome

AF:

0.997

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.996

GnomAD4 genome

AF:

0.981

AC:

149177

AN:

152046

Hom.:

73235

Cov.:

AF XY:

0.982

AC XY:

72985

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.934

Gnomad4 AMR

AF:

0.994

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.988

Alfa

AF:

0.939

Hom.:

20876

Bravo

AF:

0.978

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

1.00

AC:

3854

ESP6500AA

AF:

0.936

AC:

4120

ESP6500EA

AF:

1.00

AC:

8594

ExAC

AF:

0.994

AC:

120154

Asia WGS

AF:

0.994

AC:

3456

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.60

CADD

Benign

3.5

DANN

Benign

0.70

DEOGEN2

Benign

0.0024

T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00021

LIST_S2

Benign

0.075

T;.;T

MetaRNN

Benign

6.6e-7

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

3.3

N;N;N

REVEL

Benign

0.025

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.13

MutPred

0.36

Gain of disorder (P = 0.0063);Gain of disorder (P = 0.0063);.;

MPC

0.049

ClinPred

0.0036

GERP RS

1.1

Varity_R

0.082

gMVP

0.11

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

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