rs1499511

chr11-36066303-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_174902.4(LDLRAD3):c.194-15350T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 151,870 control chromosomes in the GnomAD database, including 34,852 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 0.67 (34852 hom., cov: 30)
• Consequence: LDLRAD3 NM_174902.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.714

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]

LOC101928510 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LDLRAD3	NM_174902.4	c.194-15350T>C		intron_variant		ENST00000315571.6
LOC101928510	NR_135064.1	n.1116A>G		non_coding_transcript_exon_variant	2/2
LDLRAD3	NM_001304263.2	c.47-15350T>C		intron_variant
LDLRAD3	NM_001304264.2	c.-286-15350T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDLRAD3	ENST00000315571.6	c.194-15350T>C		intron_variant		1	NM_174902.4	P1
LDLRAD3	ENST00000528989.5	c.47-15350T>C		intron_variant		1
LDLRAD3	ENST00000524419.5	c.47-15350T>C		intron_variant		5
LDLRAD3	ENST00000532490.1	n.148-15350T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101375 AN: 151752 Hom.: 34804 Cov.: 30

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.668 AC: 101483 AN: 151870 Hom.: 34852 Cov.: 30 AF XY: 0.667 AC XY: 49493 AN XY: 74206

Gnomad4 AFR AF: 0.845

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.636

Alfa AF: 0.595 Hom.: 35785

Bravo AF: 0.677

Asia WGS AF: 0.676 AC: 2346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	1.8
Dann	Benign	0.77

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: rs1499511; hg19: chr11-36087853;