Variant chr11-36229224-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_174902.4(LDLRAD3):c.865G>T(p.Asp289Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0011 in 1,613,740 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 12 hom. )

Consequence

LDLRAD3
NM_174902.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.67

Variant links:

Genes affected

LDLRAD3 (HGNC:27046): (low density lipoprotein receptor class A domain containing 3) Predicted to enable amyloid-beta binding activity. Predicted to act upstream of or within receptor-mediated endocytosis and regulation of protein processing. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

LDLRAD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008576393).

BP6

Variant 11-36229224-G-T is Benign according to our data. Variant chr11-36229224-G-T is described in ClinVar as [Benign]. Clinvar id is 785887.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00103 (1501/1461880) while in subpopulation AMR AF= 0.0216 (966/44724). AF 95% confidence interval is 0.0205. There are 12 homozygotes in gnomad4_exome. There are 635 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LDLRAD3	NM_174902.4 linkuse as main transcript	c.865G>T	p.Asp289Tyr	missense_variant	6/6	ENST00000315571.6
LDLRAD3	NM_001304263.2 linkuse as main transcript	c.718G>T	p.Asp240Tyr	missense_variant	5/5
LDLRAD3	NM_001304264.2 linkuse as main transcript	c.502G>T	p.Asp168Tyr	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDLRAD3	ENST00000315571.6 linkuse as main transcript	c.865G>T	p.Asp289Tyr	missense_variant	6/6	1	NM_174902.4	P1	Q86YD5-1

Frequencies

GnomAD3 genomes

AF:

0.00183

AC:

277

AN:

151738

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000315

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00935

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00381

AC:

958

AN:

251396

Hom.:

AF XY:

0.00287

AC XY:

390

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0221

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00897

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00103

AC:

1501

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

635

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0216

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0106

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

AF:

0.00182

AC:

276

AN:

151860

Hom.:

Cov.:

AF XY:

0.00221

AC XY:

164

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00917

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.000221

Hom.:

Bravo

AF:

0.00263

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00295

AC:

358

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

D;D;D

MetaRNN

Benign

0.0086

T;T;T

MetaSVM

Uncertain

0.77

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.2

N;N;D

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

1.0, 0.98

.;D;D

Vest4

0.63

MVP

0.85

MPC

0.54

ClinPred

0.054

GERP RS

5.2

Varity_R

0.52

gMVP

0.49

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