Genetic Variant LDLRAD1:p.Arg169Pro (chr1-54009094-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001010978.4(LDLRAD1):c.506G>C(p.Arg169Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R169G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LDLRAD1
NM_001010978.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.378

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.065849215).

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.506G>C	p.Arg169Pro	missense	Exon 6 of 6	NP_001010978.2	Q5T700-1
LDLRAD1	NM_001276392.2		c.389G>C	p.Arg130Pro	missense	Exon 4 of 4	NP_001263321.1	Q5T700-2
LDLRAD1	NM_001276393.2		c.377G>C	p.Arg126Pro	missense	Exon 5 of 5	NP_001263322.1	Q5T700-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDLRAD1	ENST00000371360.2	TSL:1 MANE Select	c.506G>C	p.Arg169Pro	missense	Exon 6 of 6	ENSP00000360411.1	Q5T700-1
LDLRAD1	ENST00000420619.5	TSL:1	c.389G>C	p.Arg130Pro	missense	Exon 4 of 4	ENSP00000411017.1	Q5T700-2
LDLRAD1	ENST00000545928.5	TSL:1	c.377G>C	p.Arg126Pro	missense	Exon 5 of 5	ENSP00000445871.1	Q5T700-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111960

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Benign

6.6

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.015

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.57

M_CAP

Benign

0.034

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.80

PhyloP100

-0.38

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.73

REVEL

Benign

0.28

Sift

Benign

0.16

Sift4G

Benign

0.34

Polyphen

0.0010

Vest4

0.11

MutPred

0.52

Gain of glycosylation at S172 (P = 0.0448)

MVP

0.32

MPC

0.056

ClinPred

0.29

GERP RS

-0.94

Varity_R

0.18

gMVP

0.74

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over