rs16928224

Positions:

• chr11-36007208-A-G

Variant summary

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

The NM_174902.4(LDLRAD3):​c.47-28895A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 152,260 control chromosomes in the GnomAD database, including 189 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 0.044 (189 hom., cov: 33)
• Consequence: LDLRAD3 NM_174902.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.658

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDLRAD3	NM_174902.4	c.47-28895A>G		intron_variant		ENST00000315571.6	NP_777562.1
LDLRAD3	NM_001304263.2	c.46+63064A>G		intron_variant			NP_001291192.1
LDLRAD3	NM_001304264.2	c.-287+63064A>G		intron_variant			NP_001291193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDLRAD3	ENST00000315571.6	c.47-28895A>G		intron_variant		1	NM_174902.4	ENSP00000318607	P1
LDLRAD3	ENST00000528989.5	c.46+63064A>G		intron_variant		1		ENSP00000433954
LDLRAD3	ENST00000524419.5	c.46+63064A>G		intron_variant		5		ENSP00000434313
LDLRAD3	ENST00000532490.1	n.147+6022A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6751 AN: 152142 Hom.: 186 Cov.: 33

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0780

Gnomad ASJ AF: 0.00750

Gnomad EAS AF: 0.0246

Gnomad SAS AF: 0.0526

Gnomad FIN AF: 0.0372

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0378

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

GnomAD4 genome AF: 0.0445 AC: 6773 AN: 152260 Hom.: 189 Cov.: 33 AF XY: 0.0445 AC XY: 3310 AN XY: 74440

Gnomad4 AFR AF: 0.0369

Gnomad4 AMR AF: 0.0783

Gnomad4 ASJ AF: 0.00750

Gnomad4 EAS AF: 0.0245

Gnomad4 SAS AF: 0.0539

Gnomad4 FIN AF: 0.0372

Gnomad4 NFE AF: 0.0462

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0448 Hom.: 198

Bravo AF: 0.0469

Asia WGS AF: 0.0530 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.4
DANN	Benign	0.36

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: rs16928224; hg19: chr11-36028758;