Variant 18-13621231-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000359446.11(LDLRAD4):c.296G>A(p.Arg99His) variant causes a missense change. The variant allele was found at a frequency of 0.00732 in 1,613,766 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0057 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0075 ( 48 hom. )

Consequence

LDLRAD4
ENST00000359446.11 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.34

Variant links:

Genes affected

LDLRAD4 (HGNC:1224): (low density lipoprotein receptor class A domain containing 4) Enables R-SMAD binding activity. Involved in negative regulation of cell migration; negative regulation of epithelial to mesenchymal transition; and negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway. Located in early endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

LDLRAD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0077394545).

BP6

Variant 18-13621231-G-A is Benign according to our data. Variant chr18-13621231-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648606.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDLRAD4	NM_001378100.1 linkuse as main transcript	c.296G>A	p.Arg99His	missense_variant	5/7	ENST00000359446.11	NP_001365029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDLRAD4	ENST00000359446.11 linkuse as main transcript	c.296G>A	p.Arg99His	missense_variant	5/7	1	NM_001378100.1	ENSP00000352420	P1	O15165-1

Frequencies

GnomAD3 genomes

AF:

0.00574

AC:

874

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0133

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00898

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00521

AC:

1306

AN:

250744

Hom.:

AF XY:

0.00503

AC XY:

682

AN XY:

135706

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0114

Gnomad NFE exome

AF:

0.00815

Gnomad OTH exome

AF:

0.00506

GnomAD4 exome

AF:

0.00749

AC:

10940

AN:

1461418

Hom.:

Cov.:

AF XY:

0.00708

AC XY:

5149

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00217

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.0107

Gnomad4 NFE exome

AF:

0.00888

Gnomad4 OTH exome

AF:

0.00558

GnomAD4 genome

AF:

0.00573

AC:

873

AN:

152348

Hom.:

Cov.:

AF XY:

0.00534

AC XY:

398

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0133

Gnomad4 NFE

AF:

0.00897

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00732

Hom.:

Bravo

AF:

0.00464

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00791

AC:

ExAC

AF:

0.00507

AC:

616

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00731

EpiControl

AF:

0.00848

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

LDLRAD4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.40

.;T;.;.;.;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.92

D;D;D;D;D;D

MetaRNN

Benign

0.0077

T;T;T;T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.7

M;M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.8

D;D;.;.;.;.

REVEL

Benign

0.28

Sift

Uncertain

0.0010

D;D;.;.;.;.

Sift4G

Uncertain

0.0060

D;D;D;D;D;D

Polyphen

1.0

D;D;.;.;.;.

Vest4

0.37

MVP

0.68

ClinPred

0.019

GERP RS

3.8

Varity_R

0.44

gMVP

0.67

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over