rs12361738

Positions:

• chr11-36075419-G-C
• chr11-36075419-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.194-6234G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,968 control chromosomes in the GnomAD database, including 15,702 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 0.45 (15702 hom., cov: 32)
• Consequence: LDLRAD3 NM_174902.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.883

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LDLRAD3	NM_174902.4	c.194-6234G>C		intron_variant		ENST00000315571.6
LOC101928510	NR_135064.1	n.157+2326C>G		intron_variant, non_coding_transcript_variant
LDLRAD3	NM_001304263.2	c.47-6234G>C		intron_variant
LDLRAD3	NM_001304264.2	c.-286-6234G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDLRAD3	ENST00000315571.6	c.194-6234G>C		intron_variant		1	NM_174902.4	P1
LDLRAD3	ENST00000528989.5	c.47-6234G>C		intron_variant		1
LDLRAD3	ENST00000524419.5	c.47-6234G>C		intron_variant		5
LDLRAD3	ENST00000532490.1	n.148-6234G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68634 AN: 151848 Hom.: 15678 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.452 AC: 68704 AN: 151968 Hom.: 15702 Cov.: 32 AF XY: 0.453 AC XY: 33627 AN XY: 74260

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.470

Alfa AF: 0.320 Hom.: 816

Bravo AF: 0.456

Asia WGS AF: 0.391 AC: 1364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.63

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: rs12361738; hg19: chr11-36096969;