rs16928224

Variant names:

• chr11-36007208-A-G
• rs16928224
• NM_174902.4:c.47-28895A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174902.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDLRAD3	NM_174902.4	MANE Select	c.47-28895A>G		intron	N/A	NP_777562.1	Q86YD5-1
	LDLRAD3	NM_001304263.2		c.46+63064A>G		intron	N/A	NP_001291192.1	Q86YD5-2
	LDLRAD3	NM_001304264.2		c.-287+63064A>G		intron	N/A	NP_001291193.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDLRAD3	ENST00000315571.6	TSL:1 MANE Select	c.47-28895A>G		intron	N/A	ENSP00000318607.5	Q86YD5-1
	LDLRAD3	ENST00000528989.5	TSL:1	c.46+63064A>G		intron	N/A	ENSP00000433954.1	Q86YD5-2
	LDLRAD3	ENST00000872891.1		c.47-28895A>G		intron	N/A	ENSP00000542950.1

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

African (AFR) AF: 0.0369 AC: 1533 AN: 41558

American (AMR) AF: 0.0783 AC: 1198 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00750 AC: 26 AN: 3466

East Asian (EAS) AF: 0.0245 AC: 127 AN: 5184

South Asian (SAS) AF: 0.0539 AC: 260 AN: 4822

European-Finnish (FIN) AF: 0.0372 AC: 394 AN: 10598

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0462 AC: 3146 AN: 68022

Other (OTH) AF: 0.0388 AC: 82 AN: 2112

Alfa AF: 0.0463 Hom.: 272

Bravo AF: 0.0469

Asia WGS AF: 0.0530 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.4
DANN	Benign	0.36
PhyloP100		0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16928224; hg19: chr11-36028758;