rs262404

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-36010043-G-A
• chr11-36010043-G-C
• chr11-36010043-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]

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

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 rank	MANE	Protein	UniProt
LDLRAD3	NM_174902.4	c.47-26060G>A		intron_variant	Intron 1 of 5	ENST00000315571.6	NP_777562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDLRAD3	ENST00000315571.6	c.47-26060G>A		intron_variant	Intron 1 of 5	1	NM_174902.4	ENSP00000318607.5

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;