rs262421

Variant names:

• chr11-36016809-C-T
• rs262421
• NM_174902.4:c.47-19294C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174902.4(LDLRAD3):​c.47-19294C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,126 control chromosomes in the GnomAD database, including 15,581 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 0.43 (15581 hom., cov: 33)
• Consequence: LDLRAD3 NM_174902.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDLRAD3	NM_174902.4	c.47-19294C>T		intron_variant	Intron 1 of 5	ENST00000315571.6	NP_777562.1
LDLRAD3	NM_001304263.2	c.47-64844C>T		intron_variant	Intron 1 of 4		NP_001291192.1
LDLRAD3	NM_001304264.2	c.-286-64844C>T		intron_variant	Intron 1 of 5		NP_001291193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDLRAD3	ENST00000315571.6	c.47-19294C>T		intron_variant	Intron 1 of 5	1	NM_174902.4	ENSP00000318607.5
LDLRAD3	ENST00000528989.5	c.47-64844C>T		intron_variant	Intron 1 of 4	1		ENSP00000433954.1
LDLRAD3	ENST00000524419.5	c.47-64844C>T		intron_variant	Intron 1 of 5	5		ENSP00000434313.1
LDLRAD3	ENST00000532490.1	n.147+15623C>T		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65373 AN: 152008 Hom.: 15575 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.430 AC: 65396 AN: 152126 Hom.: 15581 Cov.: 33 AF XY: 0.427 AC XY: 31750 AN XY: 74352

African (AFR) AF: 0.217 AC: 9007 AN: 41530

American (AMR) AF: 0.484 AC: 7397 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1814 AN: 3472

East Asian (EAS) AF: 0.303 AC: 1570 AN: 5186

South Asian (SAS) AF: 0.408 AC: 1966 AN: 4818

European-Finnish (FIN) AF: 0.500 AC: 5285 AN: 10560

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36821 AN: 67958

Other (OTH) AF: 0.454 AC: 959 AN: 2114

Alfa AF: 0.512 Hom.: 12167

Bravo AF: 0.422

Asia WGS AF: 0.347 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.24
DANN	Benign	0.71
PhyloP100		-0.88
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: rs262421; hg19: chr11-36038359;