rs12361738

Variant names:

• chr11-36075419-G-C
• rs12361738
• NM_174902.4:c.194-6234G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-36075419-G-C
• chr11-36075419-G-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.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
• Publications: 5 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]

LOC101928510 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LDLRAD3	NM_174902.4	c.194-6234G>C		intron_variant	Intron 2 of 5	ENST00000315571.6	NP_777562.1
LDLRAD3	NM_001304263.2	c.47-6234G>C		intron_variant	Intron 1 of 4		NP_001291192.1
LDLRAD3	NM_001304264.2	c.-286-6234G>C		intron_variant	Intron 1 of 5		NP_001291193.1
LOC101928510	NR_135064.1	n.157+2326C>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDLRAD3	ENST00000315571.6	c.194-6234G>C		intron_variant	Intron 2 of 5	1	NM_174902.4	ENSP00000318607.5
LDLRAD3	ENST00000528989.5	c.47-6234G>C		intron_variant	Intron 1 of 4	1		ENSP00000433954.1
LDLRAD3	ENST00000524419.5	c.47-6234G>C		intron_variant	Intron 1 of 5	5		ENSP00000434313.1
LDLRAD3	ENST00000532490.1	n.148-6234G>C		intron_variant	Intron 2 of 4	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

African (AFR) AF: 0.496 AC: 20560 AN: 41454

American (AMR) AF: 0.462 AC: 7052 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1751 AN: 3470

East Asian (EAS) AF: 0.378 AC: 1953 AN: 5162

South Asian (SAS) AF: 0.422 AC: 2033 AN: 4812

European-Finnish (FIN) AF: 0.473 AC: 4984 AN: 10542

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28849 AN: 67940

Other (OTH) AF: 0.470 AC: 991 AN: 2108

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
PhyloP100		0.88
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: rs12361738; hg19: chr11-36096969;