11-36010043-G-A

Variant names:

• chr11-36010043-G-A
• rs262404
• NM_174902.4:c.47-26060G>A

Variant summary

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

The NM_174902.4(LDLRAD3):​c.47-26060G>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
• Publications: 3 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]

MIR3973 (HGNC:41756): (microRNA 3973) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174902.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDLRAD3	NM_174902.4	MANE Select	c.47-26060G>A		intron	N/A	NP_777562.1	Q86YD5-1
	LDLRAD3	NM_001304263.2		c.46+65899G>A		intron	N/A	NP_001291192.1	Q86YD5-2
	LDLRAD3	NM_001304264.2		c.-287+65899G>A		intron	N/A	NP_001291193.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDLRAD3	ENST00000315571.6	TSL:1 MANE Select	c.47-26060G>A		intron	N/A	ENSP00000318607.5	Q86YD5-1
	LDLRAD3	ENST00000528989.5	TSL:1	c.46+65899G>A		intron	N/A	ENSP00000433954.1	Q86YD5-2
	LDLRAD3	ENST00000872891.1		c.47-26060G>A		intron	N/A	ENSP00000542950.1

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

African (AFR) AF: 0.703 AC: 52 AN: 74

American (AMR) AF: 0.750 AC: 6 AN: 8

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 4 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.947 AC: 89 AN: 94

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AF: 0.960 AC: 1564 AN: 1630

European-Non Finnish (NFE) AF: 0.934 AC: 170 AN: 182

Other (OTH) AF: 0.879 AC: 167 AN: 190

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

African (AFR) AF: 0.693 AC: 28758 AN: 41476

American (AMR) AF: 0.895 AC: 13707 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 3443 AN: 3472

East Asian (EAS) AF: 0.976 AC: 5054 AN: 5180

South Asian (SAS) AF: 0.945 AC: 4551 AN: 4816

European-Finnish (FIN) AF: 0.963 AC: 10208 AN: 10600

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

European-Non Finnish (NFE) AF: 0.952 AC: 64790 AN: 68044

Other (OTH) AF: 0.899 AC: 1896 AN: 2110

Alfa AF: 0.921 Hom.: 17830

Bravo AF: 0.865

Asia WGS AF: 0.928 AC: 3225 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.44
PhyloP100		-1.2
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: rs262404; hg19: chr11-36031593;