rs262407

Positions:

• chr11-36007825-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.47-28278C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 152,218 control chromosomes in the GnomAD database, including 60,252 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 0.88 (60252 hom., cov: 32)
• Consequence: LDLRAD3 NM_174902.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDLRAD3	NM_174902.4	c.47-28278C>T		intron_variant		ENST00000315571.6	NP_777562.1
LDLRAD3	NM_001304263.2	c.46+63681C>T		intron_variant			NP_001291192.1
LDLRAD3	NM_001304264.2	c.-287+63681C>T		intron_variant			NP_001291193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDLRAD3	ENST00000315571.6	c.47-28278C>T		intron_variant		1	NM_174902.4	ENSP00000318607	P1
LDLRAD3	ENST00000528989.5	c.46+63681C>T		intron_variant		1		ENSP00000433954
LDLRAD3	ENST00000524419.5	c.46+63681C>T		intron_variant		5		ENSP00000434313
LDLRAD3	ENST00000532490.1	n.147+6639C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134411 AN: 152100 Hom.: 60235 Cov.: 32

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.952

Gnomad OTH AF: 0.904

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

GnomAD4 genome AF: 0.883 AC: 134484 AN: 152218 Hom.: 60252 Cov.: 32 AF XY: 0.886 AC XY: 65927 AN XY: 74428

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.992

Gnomad4 EAS AF: 0.980

Gnomad4 SAS AF: 0.946

Gnomad4 FIN AF: 0.963

Gnomad4 NFE AF: 0.952

Gnomad4 OTH AF: 0.903

Alfa AF: 0.948 Hom.: 125459

Bravo AF: 0.872

Asia WGS AF: 0.931 AC: 3237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.30
DANN	Benign	0.82

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: rs262407; hg19: chr11-36029375;