dbSNP rs146139497: LDLRAD3:p.Ala46Thr (chr11-36036192-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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

Publications

7 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 710803.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174902.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDLRAD3	NM_174902.4	MANE Select	c.136G>A	p.Ala46Thr	missense	Exon 2 of 6	NP_777562.1	Q86YD5-1
LDLRAD3	NM_001304263.2		c.47-45461G>A		intron	N/A	NP_001291192.1	Q86YD5-2
LDLRAD3	NM_001304264.2		c.-286-45461G>A		intron	N/A	NP_001291193.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDLRAD3	ENST00000315571.6	TSL:1 MANE Select	c.136G>A	p.Ala46Thr	missense	Exon 2 of 6	ENSP00000318607.5	Q86YD5-1
LDLRAD3	ENST00000528989.5	TSL:1	c.47-45461G>A		intron	N/A	ENSP00000433954.1	Q86YD5-2
LDLRAD3	ENST00000872891.1		c.136G>A	p.Ala46Thr	missense	Exon 2 of 6	ENSP00000542950.1

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

GnomAD2 exomes

AF:

0.00508

AC:

1277

AN:

251348

AF XY:

0.00492

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 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

African (AFR)

AF:

0.000239

AC:

AN:

33480

American (AMR)

AF:

0.000559

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0453

AC:

2420

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000453

AC:

504

AN:

1112006

Other (OTH)

AF:

0.00278

AC:

168

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

183

367

550

734

917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00434

AC:

661

AN:

152298

Hom.:

Cov.:

AF XY:

0.00611

AC XY:

455

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41566

American (AMR)

AF:

0.000457

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0490

AC:

520

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00178

AC:

121

AN:

68016

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

109

146

182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00125

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

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

PhyloP100

5.2

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

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over