rs1358054

Positions:

• chr11-36185122-C-A
• chr11-36185122-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174902.4(LDLRAD3):​c.455-41963C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,004 control chromosomes in the GnomAD database, including 16,124 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (16124 hom., cov: 32)
• Consequence: LDLRAD3 NM_174902.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.73

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDLRAD3	NM_174902.4	c.455-41963C>A		intron_variant		ENST00000315571.6	NP_777562.1
LDLRAD3	NM_001304263.2	c.308-41963C>A		intron_variant			NP_001291192.1
LDLRAD3	NM_001304264.2	c.91+1014C>A		intron_variant			NP_001291193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDLRAD3	ENST00000315571.6	c.455-41963C>A		intron_variant		1	NM_174902.4	ENSP00000318607	P1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68687 AN: 151886 Hom.: 16114 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.450

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.452 AC: 68725 AN: 152004 Hom.: 16124 Cov.: 32 AF XY: 0.456 AC XY: 33857 AN XY: 74292

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.451

Alfa AF: 0.366 Hom.: 1345

Bravo AF: 0.433

Asia WGS AF: 0.541 AC: 1878 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs1358054; hg19: chr11-36206672;