chr11-36185122-C-A

Variant names:

• chr11-36185122-C-A
• rs1358054
• NM_174902.4:c.455-41963C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.91).
• 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 rank	MANE	Protein	UniProt
LDLRAD3	NM_174902.4	c.455-41963C>A		intron_variant	Intron 4 of 5	ENST00000315571.6	NP_777562.1
LDLRAD3	NM_001304263.2	c.308-41963C>A		intron_variant	Intron 3 of 4		NP_001291192.1
LDLRAD3	NM_001304264.2	c.91+1014C>A		intron_variant	Intron 4 of 5		NP_001291193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDLRAD3	ENST00000315571.6	c.455-41963C>A		intron_variant	Intron 4 of 5	1	NM_174902.4	ENSP00000318607.5

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

African (AFR) AF: 0.337 AC: 13984 AN: 41440

American (AMR) AF: 0.407 AC: 6221 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1588 AN: 3464

East Asian (EAS) AF: 0.423 AC: 2188 AN: 5174

South Asian (SAS) AF: 0.547 AC: 2635 AN: 4814

European-Finnish (FIN) AF: 0.554 AC: 5841 AN: 10548

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34658 AN: 67966

Other (OTH) AF: 0.451 AC: 950 AN: 2106

Alfa AF: 0.477 Hom.: 25709

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
PhyloP100		-3.7
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: rs1358054; hg19: chr11-36206672;