rs262421

Positions:

• chr11-36016809-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.47-19294C>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

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=-0.87).
• 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/exons	MANE	UniProt
LDLRAD3	NM_174902.4	c.47-19294C>T		intron_variant		ENST00000315571.6
LDLRAD3	NM_001304263.2	c.47-64844C>T		intron_variant
LDLRAD3	NM_001304264.2	c.-286-64844C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDLRAD3	ENST00000315571.6	c.47-19294C>T		intron_variant		1	NM_174902.4	P1
LDLRAD3	ENST00000528989.5	c.47-64844C>T		intron_variant		1
LDLRAD3	ENST00000524419.5	c.47-64844C>T		intron_variant		5
LDLRAD3	ENST00000532490.1	n.147+15623C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.454

Alfa AF: 0.514 Hom.: 11084

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

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: rs262421; hg19: chr11-36038359;