chr11-36007825-C-T

Variant names:

• chr11-36007825-C-T
• rs262407
• NM_174902.4:c.47-28278C>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.47-28278C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 152,218 control chromosomes in the GnomAD database, including 60,252 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 (60252 hom., cov: 32)
• Consequence: LDLRAD3 NM_174902.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDLRAD3	NM_174902.4	c.47-28278C>T		intron_variant	Intron 1 of 5	ENST00000315571.6	NP_777562.1
LDLRAD3	NM_001304263.2	c.46+63681C>T		intron_variant	Intron 1 of 4		NP_001291192.1
LDLRAD3	NM_001304264.2	c.-287+63681C>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.47-28278C>T		intron_variant	Intron 1 of 5	1	NM_174902.4	ENSP00000318607.5
LDLRAD3	ENST00000528989.5	c.46+63681C>T		intron_variant	Intron 1 of 4	1		ENSP00000433954.1
LDLRAD3	ENST00000524419.5	c.46+63681C>T		intron_variant	Intron 1 of 5	5		ENSP00000434313.1
LDLRAD3	ENST00000532490.1	n.147+6639C>T		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134411 AN: 152100 Hom.: 60235 Cov.: 32

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.952

Gnomad OTH AF: 0.904

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

GnomAD4 genome AF: 0.883 AC: 134484 AN: 152218 Hom.: 60252 Cov.: 32 AF XY: 0.886 AC XY: 65927 AN XY: 74428

African (AFR) AF: 0.713 AC: 29584 AN: 41492

American (AMR) AF: 0.898 AC: 13734 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 3441 AN: 3470

East Asian (EAS) AF: 0.980 AC: 5070 AN: 5176

South Asian (SAS) AF: 0.946 AC: 4553 AN: 4814

European-Finnish (FIN) AF: 0.963 AC: 10222 AN: 10618

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.952 AC: 64782 AN: 68024

Other (OTH) AF: 0.903 AC: 1911 AN: 2116

Alfa AF: 0.930 Hom.: 191304

Bravo AF: 0.872

Asia WGS AF: 0.931 AC: 3237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.30
DANN	Benign	0.82
PhyloP100		-0.55
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: rs262407; hg19: chr11-36029375;