Variant chr11-36036192-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 NM_174902.4(LDLRAD3):c.136G>A(p.Ala46Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00235 in 1,614,152 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 56 hom. )

Consequence

LDLRAD3
NM_174902.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.16

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009468585).

BP6

Variant 11-36036192-G-A is Benign according to our data. Variant chr11-36036192-G-A is described in ClinVar as [Benign]. Clinvar id is 710803.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LDLRAD3	NM_174902.4 linkuse as main transcript	c.136G>A	p.Ala46Thr	missense_variant	2/6	ENST00000315571.6
LDLRAD3	NM_001304263.2 linkuse as main transcript	c.47-45461G>A		intron_variant
LDLRAD3	NM_001304264.2 linkuse as main transcript	c.-286-45461G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDLRAD3	ENST00000315571.6 linkuse as main transcript	c.136G>A	p.Ala46Thr	missense_variant	2/6	1	NM_174902.4	P1	Q86YD5-1
LDLRAD3	ENST00000528989.5 linkuse as main transcript	c.47-45461G>A		intron_variant		1			Q86YD5-2
LDLRAD3	ENST00000524419.5 linkuse as main transcript	c.47-45461G>A		intron_variant		5
LDLRAD3	ENST00000532490.1 linkuse as main transcript	n.147+35006G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00434

AC:

661

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0490

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00178

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00508

AC:

1277

AN:

251348

Hom.:

AF XY:

0.00492

AC XY:

669

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0448

Gnomad NFE exome

AF:

0.00204

Gnomad OTH exome

AF:

0.00831

GnomAD4 exome

AF:

0.00214

AC:

3127

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

1505

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0453

Gnomad4 NFE exome

AF:

0.000453

Gnomad4 OTH exome

AF:

0.00278

GnomAD4 genome

AF:

0.00434

AC:

661

AN:

152298

Hom.:

Cov.:

AF XY:

0.00611

AC XY:

455

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0490

Gnomad4 NFE

AF:

0.00178

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.000510

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00484

AC:

588

EpiCase

AF:

0.000164

EpiControl

AF:

0.000593

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

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.50

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0095

MetaSVM

Benign

-0.49

MutationAssessor

Benign

0.42

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.91

REVEL

Benign

0.28

Sift

Benign

0.070

Sift4G

Benign

0.23

Polyphen

0.0030

Vest4

0.41

MVP

0.44

MPC

0.33

ClinPred

0.046

GERP RS

-0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.040

gMVP

0.39

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