rs262404

chr11-36010043-G-Achr11-36010043-G-Cchr11-36010043-G-T

Variant summary

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

The NM_174902.4(LDLRAD3):c.47-26060G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 154,398 control chromosomes in the GnomAD database, including 60,592 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 0.88 (59621 hom., cov: 32)
  • Exomes 𝑓: 0.94 (971 hom.)
• Consequence: LDLRAD3 NM_174902.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LDLRAD3	NM_174902.4	c.47-26060G>A		intron_variant		ENST00000315571.6
LDLRAD3	NM_001304263.2	c.46+65899G>A		intron_variant
LDLRAD3	NM_001304264.2	c.-287+65899G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDLRAD3	ENST00000315571.6	c.47-26060G>A		intron_variant		1	NM_174902.4	P1
LDLRAD3	ENST00000528989.5	c.46+65899G>A		intron_variant		1
LDLRAD3	ENST00000524419.5	c.46+65899G>A		intron_variant		5
LDLRAD3	ENST00000532490.1	n.147+8857G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133533 AN: 152096 Hom.: 59610 Cov.: 32

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.952

Gnomad OTH AF: 0.899

GnomAD4 exome AF: 0.940 AC: 2054 AN: 2184 Hom.: 971 AF XY: 0.931 AC XY: 1011 AN XY: 1086

Gnomad4 AFR exome AF: 0.703

Gnomad4 AMR exome AF: 0.750

Gnomad4 ASJ exome AF: 1.00

Gnomad4 SAS exome AF: 0.947

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.934

Gnomad4 OTH exome AF: 0.879

GnomAD4 genome AF: 0.878 AC: 133594 AN: 152214 Hom.: 59621 Cov.: 32 AF XY: 0.880 AC XY: 65510 AN XY: 74424

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.895

Gnomad4 ASJ AF: 0.992

Gnomad4 EAS AF: 0.976

Gnomad4 SAS AF: 0.945

Gnomad4 FIN AF: 0.963

Gnomad4 NFE AF: 0.952

Gnomad4 OTH AF: 0.899

Alfa AF: 0.924 Hom.: 8865

Bravo AF: 0.865

Asia WGS AF: 0.928 AC: 3225 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.13
Dann	Benign	0.44

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: rs262404; hg19: chr11-36031593;