Variant 11-36098452-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_174902.4(LDLRAD3):c.445A>C(p.Ser149Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,614,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

LDLRAD3
NM_174902.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.81

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:

LDLRAD3 (HGNC:):

LDLRAD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009123355).

BP6

Variant 11-36098452-A-C is Benign according to our data. Variant chr11-36098452-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 726881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDLRAD3	NM_174902.4 linkuse as main transcript	c.445A>C	p.Ser149Arg	missense_variant	4/6	ENST00000315571.6	NP_777562.1	Q86YD5-1
LDLRAD3	NM_001304263.2 linkuse as main transcript	c.298A>C	p.Ser100Arg	missense_variant	3/5		NP_001291192.1	Q86YD5-2
LDLRAD3	NM_001304264.2 linkuse as main transcript	c.-35A>C		5_prime_UTR_variant	3/6		NP_001291193.1	Q86YD5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LDLRAD3	ENST00000315571.6 linkuse as main transcript	c.445A>C	p.Ser149Arg	missense_variant	4/6	1	NM_174902.4	ENSP00000318607.5	Q86YD5-1
LDLRAD3	ENST00000528989.5 linkuse as main transcript	c.298A>C	p.Ser100Arg	missense_variant	3/5	1		ENSP00000433954.1	Q86YD5-2
LDLRAD3	ENST00000524419.5 linkuse as main transcript	c.298A>C	p.Ser100Arg	missense_variant	3/6	5		ENSP00000434313.1	E9PR86
LDLRAD3	ENST00000532490.1 linkuse as main transcript	n.399A>C		non_coding_transcript_exon_variant	4/5	4

Frequencies

GnomAD3 genomes

AF:

0.000690

AC:

105

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000227

AC:

AN:

250582

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

135500

show subpopulations

Gnomad AFR exome

AF:

0.00326

Gnomad AMR exome

AF:

0.000116

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000800

AC:

117

AN:

1461868

Hom.:

Cov.:

AF XY:

0.0000660

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00290

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000683

AC:

104

AN:

152352

Hom.:

Cov.:

AF XY:

0.000617

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00228

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000172

Hom.:

Bravo

AF:

0.000963

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000296

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

.;.;T

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

D;T;D

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.0091

T;T;T

MetaSVM

Uncertain

0.082

MutationAssessor

Benign

1.4

.;.;L

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.2

N;N;N

REVEL

Uncertain

0.46

Sift

Uncertain

0.010

D;D;D

Sift4G

Benign

0.062

T;D;D

Polyphen

0.84

.;.;P

Vest4

0.59

MutPred

0.23

.;.;Loss of phosphorylation at S149 (P = 0.023);

MVP

0.82

MPC

0.30

ClinPred

0.11

GERP RS

5.0

Varity_R

0.31

gMVP

0.57

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