rs6789

Positions:

• chr4-3512968-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_002337.4(LRPAP1):​c.*6T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,605,270 control chromosomes in the GnomAD database, including 90,580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.33 (8484 hom., cov: 34)
  • Exomes 𝑓: 0.33 (82096 hom.)
• Consequence: LRPAP1 NM_002337.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298

Genes affected

LRPAP1 (HGNC:6701): (LDL receptor related protein associated protein 1) This gene encodes a protein that interacts with the low density lipoprotein (LDL) receptor-related protein and facilitates its proper folding and localization by preventing the binding of ligands. Mutations in this gene have been identified in individuals with myopia 23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 4-3512968-A-G is Benign according to our data. Variant chr4-3512968-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRPAP1	NM_002337.4	c.*6T>C		3_prime_UTR_variant	8/8	ENST00000650182.1
LRPAP1	NR_110005.2	n.1043T>C		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRPAP1	ENST00000650182.1	c.*6T>C		3_prime_UTR_variant	8/8		NM_002337.4	P1
LRPAP1	ENST00000296325.9	n.1043T>C		non_coding_transcript_exon_variant	8/8	1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49472 AN: 152044 Hom.: 8465 Cov.: 34

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.311

GnomAD3 exomes AF: 0.366 AC: 86976 AN: 237522 Hom.: 17413 AF XY: 0.365 AC XY: 46938 AN XY: 128556

Gnomad AFR exome AF: 0.271

Gnomad AMR exome AF: 0.584

Gnomad ASJ exome AF: 0.290

Gnomad EAS exome AF: 0.413

Gnomad SAS exome AF: 0.497

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.302

Gnomad OTH exome AF: 0.343

GnomAD4 exome AF: 0.328 AC: 477109 AN: 1453108 Hom.: 82096 Cov.: 33 AF XY: 0.333 AC XY: 240718 AN XY: 722226

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.573

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.413

Gnomad4 SAS exome AF: 0.508

Gnomad4 FIN exome AF: 0.243

Gnomad4 NFE exome AF: 0.308

Gnomad4 OTH exome AF: 0.330

GnomAD4 genome AF: 0.325 AC: 49528 AN: 152162 Hom.: 8484 Cov.: 34 AF XY: 0.331 AC XY: 24661 AN XY: 74408

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.309

Alfa AF: 0.315 Hom.: 10420

Bravo AF: 0.337

Asia WGS AF: 0.407 AC: 1413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.80
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6789; hg19: chr4-3514695; COSMIC: COSV56347184; COSMIC: COSV56347184;