rs140538964

Variant names:

• chr1-54009094-C-A
• NM_001010978.4:c.506G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-54009094-C-A
• chr1-54009094-C-G
• chr1-54009094-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001010978.4(LDLRAD1):​c.506G>T​(p.Arg169Leu) 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. 15/21 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089683294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDLRAD1	NM_001010978.4	c.506G>T	p.Arg169Leu	missense_variant	Exon 6 of 6	ENST00000371360.2	NP_001010978.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDLRAD1	ENST00000371360.2	c.506G>T	p.Arg169Leu	missense_variant	Exon 6 of 6	1	NM_001010978.4	ENSP00000360411.1
LDLRAD1	ENST00000420619.5	c.389G>T	p.Arg130Leu	missense_variant	Exon 4 of 4	1		ENSP00000411017.1
LDLRAD1	ENST00000545928.5	c.377G>T	p.Arg126Leu	missense_variant	Exon 5 of 5	1		ENSP00000445871.1
LDLRAD1	ENST00000371362.7	c.239G>T	p.Arg80Leu	missense_variant	Exon 4 of 4	1		ENSP00000360413.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461744 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727176

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	7.3
DANN	Benign	0.78
DEOGEN2	Benign	0.10	.;.;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.090	T;T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.9	.;.;.;L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.4	N;N;D;D
REVEL	Benign	0.26
Sift	Benign	0.32	T;D;T;T
Sift4G	Benign	0.68	T;T;T;T
Polyphen		0.082	.;.;.;B
Vest4		0.24
MutPred		0.52		.;.;.;Gain of glycosylation at S172 (P = 0.0587);
MVP		0.34
MPC		0.074
ClinPred		0.13	T
GERP RS		-0.94
Varity_R		0.11
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-54474767;