chr1-53246063-G-C

Variant names:

• chr1-53246063-G-C
• rs5177
• NM_004631.5:c.*955C>G

Variant summary

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

The NM_004631.5(LRP8):​c.*955C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,030 control chromosomes in the GnomAD database, including 9,149 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 0.32 (9148 hom., cov: 32)
  • Exomes 𝑓: 0.30 (1 hom.)
• Consequence: LRP8 NM_004631.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.659
• Publications: 27 publications found

Genes affected

LRP8 (HGNC:6700): (LDL receptor related protein 8) This gene encodes a member of the low density lipoprotein receptor (LDLR) family. Low density lipoprotein receptors are cell surface proteins that play roles in both signal transduction and receptor-mediated endocytosis of specific ligands for lysosomal degradation. The encoded protein plays a critical role in the migration of neurons during development by mediating Reelin signaling, and also functions as a receptor for the cholesterol transport protein apolipoprotein E. Expression of this gene may be a marker for major depressive disorder. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2011]

MAGOH-DT (HGNC:49539): (MAGOH divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004631.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP8	NM_004631.5	MANE Select	c.*955C>G		3_prime_UTR	Exon 19 of 19	NP_004622.2
	LRP8	NM_001018054.3		c.*955C>G		3_prime_UTR	Exon 18 of 18	NP_001018064.1
	LRP8	NM_033300.4		c.*955C>G		3_prime_UTR	Exon 17 of 17	NP_150643.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP8	ENST00000306052.12	TSL:1 MANE Select	c.*955C>G		3_prime_UTR	Exon 19 of 19	ENSP00000303634.6
	LRP8	ENST00000480045.6	TSL:5	n.*2012C>G		non_coding_transcript_exon	Exon 18 of 18	ENSP00000433554.2
	LRP8	ENST00000654834.1		n.3307C>G		non_coding_transcript_exon	Exon 13 of 13

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48279 AN: 151902 Hom.: 9143 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.300 AC: 3 AN: 10 Hom.: 1 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.318 AC: 48289 AN: 152020 Hom.: 9148 Cov.: 32 AF XY: 0.317 AC XY: 23547 AN XY: 74296

African (AFR) AF: 0.120 AC: 4986 AN: 41512

American (AMR) AF: 0.314 AC: 4800 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1094 AN: 3472

East Asian (EAS) AF: 0.488 AC: 2519 AN: 5162

South Asian (SAS) AF: 0.198 AC: 956 AN: 4820

European-Finnish (FIN) AF: 0.447 AC: 4709 AN: 10536

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28071 AN: 67924

Other (OTH) AF: 0.300 AC: 634 AN: 2110

Alfa AF: 0.251 Hom.: 758

Bravo AF: 0.302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.42
PhyloP100		0.66
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: rs5177; hg19: chr1-53711735;