Genetic Variant LDLRAD1:p.Gly11Val (chr1-54017417-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001010978.4(LDLRAD1):c.32G>T(p.Gly11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000337 in 1,602,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

LDLRAD1
NM_001010978.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.437

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02105543).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010978.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDLRAD1	NM_001010978.4	MANE Select	c.32G>T	p.Gly11Val	missense	Exon 2 of 6	NP_001010978.2	Q5T700-1
LDLRAD1	NM_001276393.2		c.32G>T	p.Gly11Val	missense	Exon 2 of 5	NP_001263322.1	Q5T700-4
LDLRAD1	NM_001276394.2		c.32G>T	p.Gly11Val	missense	Exon 2 of 4	NP_001263323.1	Q5T700-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDLRAD1	ENST00000371360.2	TSL:1 MANE Select	c.32G>T	p.Gly11Val	missense	Exon 2 of 6	ENSP00000360411.1	Q5T700-1
LDLRAD1	ENST00000545928.5	TSL:1	c.32G>T	p.Gly11Val	missense	Exon 2 of 5	ENSP00000445871.1	Q5T700-4
LDLRAD1	ENST00000371362.7	TSL:1	c.32G>T	p.Gly11Val	missense	Exon 2 of 4	ENSP00000360413.3	Q5T700-3

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.0000519

AC:

AN:

231020

AF XY:

0.0000321

show subpopulations

Gnomad AFR exome

AF:

0.000828

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000138

AC:

AN:

1450396

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

720264

show subpopulations

African (AFR)

AF:

0.000420

AC:

AN:

33308

American (AMR)

AF:

0.0000231

AC:

AN:

43366

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25822

East Asian (EAS)

AF:

0.00

AC:

AN:

39450

South Asian (SAS)

AF:

0.00

AC:

AN:

83952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52806

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000362

AC:

AN:

1105994

Other (OTH)

AF:

0.0000167

AC:

AN:

59948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000223

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.000772

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.000956

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000128

Hom.:

Bravo

AF:

0.000268

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000660

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.29

CADD

Benign

9.4

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0057

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.50

M_CAP

Benign

0.0026

MetaRNN

Benign

0.021

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PhyloP100

-0.44

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.5

REVEL

Benign

0.069

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0090

Polyphen

0.67

Vest4

0.32

MVP

0.17

MPC

0.070

ClinPred

0.043

GERP RS

0.69

Varity_R

0.077

gMVP

0.41

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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