Variant 11-36036119-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_174902.4(LDLRAD3):c.63C>A(p.Pro21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000599 in 1,613,846 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 9 hom. )

Consequence

LDLRAD3
NM_174902.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.34

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 11-36036119-C-A is Benign according to our data. Variant chr11-36036119-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 774623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.34 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LDLRAD3	NM_174902.4 linkuse as main transcript	c.63C>A	p.Pro21=	synonymous_variant	2/6	ENST00000315571.6	NP_777562.1
LDLRAD3	NM_001304263.2 linkuse as main transcript	c.47-45534C>A		intron_variant			NP_001291192.1
LDLRAD3	NM_001304264.2 linkuse as main transcript	c.-286-45534C>A		intron_variant			NP_001291193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDLRAD3	ENST00000315571.6 linkuse as main transcript	c.63C>A	p.Pro21=	synonymous_variant	2/6	1	NM_174902.4	ENSP00000318607	P1	Q86YD5-1
LDLRAD3	ENST00000528989.5 linkuse as main transcript	c.47-45534C>A		intron_variant		1		ENSP00000433954		Q86YD5-2
LDLRAD3	ENST00000524419.5 linkuse as main transcript	c.47-45534C>A		intron_variant		5		ENSP00000434313
LDLRAD3	ENST00000532490.1 linkuse as main transcript	n.147+34933C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000644

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000514

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000908

AC:

228

AN:

251024

Hom.:

AF XY:

0.00119

AC XY:

162

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000667

Gnomad ASJ exome

AF:

0.00507

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00258

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000581

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000595

AC:

869

AN:

1461570

Hom.:

Cov.:

AF XY:

0.000736

AC XY:

535

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000917

Gnomad4 ASJ exome

AF:

0.00536

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00260

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000274

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.000644

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000736

Hom.:

Bravo

AF:

0.000589

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00115

EpiControl

AF:

0.000949

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

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.12

DANN

Benign

0.71

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