Variant 1-54018097-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001010978.4(LDLRAD1):c.16C>G(p.Pro6Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,613,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P6S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

LDLRAD1
NM_001010978.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.605

Variant links:

Genes affected

LDLRAD1 (HGNC:32069): (low density lipoprotein receptor class A domain containing 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LDLRAD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008631974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDLRAD1	NM_001010978.4 linkuse as main transcript	c.16C>G	p.Pro6Ala	missense_variant	1/6	ENST00000371360.2	NP_001010978.2	Q5T700-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LDLRAD1	ENST00000371360.2 linkuse as main transcript	c.16C>G	p.Pro6Ala	missense_variant	1/6	1	NM_001010978.4	ENSP00000360411.1	Q5T700-1
LDLRAD1	ENST00000420619.5 linkuse as main transcript	c.80C>G	p.Pro27Arg	missense_variant	1/4	1		ENSP00000411017.1	Q5T700-2
LDLRAD1	ENST00000545928.5 linkuse as main transcript	c.16C>G	p.Pro6Ala	missense_variant	1/5	1		ENSP00000445871.1	Q5T700-4
LDLRAD1	ENST00000371362.7 linkuse as main transcript	c.16C>G	p.Pro6Ala	missense_variant	1/4	1		ENSP00000360413.3	Q5T700-3

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000247

AC:

AN:

251096

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00518

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000114

AC:

167

AN:

1460998

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

726842

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00487

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000138

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000630

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000189

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.16C>G (p.P6A) alteration is located in exon 1 (coding exon 1) of the LDLRAD1 gene. This alteration results from a C to G substitution at nucleotide position 16, causing the proline (P) at amino acid position 6 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0088

.;.;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.53

T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.0086

T;T;T

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.070

N;N;N

REVEL

Benign

0.069

Sift

Benign

0.063

T;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.44, 0.92

.;B;P

Vest4

0.27

MVP

0.42

MPC

0.18

ClinPred

0.074

GERP RS

1.8

Varity_R

0.038

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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