Variant 7-105974880-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_152750.5(CDHR3):c.83C>T(p.Thr28Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,613,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

CDHR3
NM_152750.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.898

Variant links:

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]

CDHR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 7-105974880-C-T is Benign according to our data. Variant chr7-105974880-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3141394.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDHR3	NM_152750.5 linkuse as main transcript	c.83C>T	p.Thr28Ile	missense_variant	2/19	ENST00000317716.14
CDHR3	NM_001301161.2 linkuse as main transcript	c.-15-6088C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDHR3	ENST00000317716.14 linkuse as main transcript	c.83C>T	p.Thr28Ile	missense_variant	2/19	1	NM_152750.5	P1	Q6ZTQ4-1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000883

AC:

AN:

249084

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000156

AC:

228

AN:

1461426

Hom.:

Cov.:

AF XY:

0.000168

AC XY:

122

AN XY:

727016

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000196

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000853

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000299

Hom.:

Bravo

AF:

0.0000642

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000362

AC:

ExAC

AF:

0.000108

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.49

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.0046

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.47

M_CAP

Benign

0.0040

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.7

REVEL

Benign

0.082

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.045

Polyphen

0.0030

Vest4

0.47

MVP

0.072

MPC

0.053

ClinPred

0.12

GERP RS

2.6

Varity_R

0.32

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: -36

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over