rs1288548

Positions:

• chr4-185378831-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018409.4(LRP2BP):​c.-645C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 985,142 control chromosomes in the GnomAD database, including 20,340 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 0.22 (4069 hom., cov: 32)
  • Exomes 𝑓: 0.20 (16271 hom.)
• Consequence: LRP2BP NM_018409.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510

Genes affected

LRP2BP (HGNC:25434): (LRP2 binding protein) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LRP2BP-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP2BP	NM_001377440.1	c.-21-624C>T		intron_variant		ENST00000505916.6	NP_001364369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP2BP	ENST00000505916.6	c.-21-624C>T		intron_variant		2	NM_001377440.1	ENSP00000426203.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33624 AN: 151952 Hom.: 4073 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.196 AC: 162900 AN: 833072 Hom.: 16271 Cov.: 31 AF XY: 0.196 AC XY: 75437 AN XY: 384694

Gnomad4 AFR exome AF: 0.355

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.198

GnomAD4 genome AF: 0.221 AC: 33628 AN: 152070 Hom.: 4069 Cov.: 32 AF XY: 0.218 AC XY: 16242 AN XY: 74352

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.205

Alfa AF: 0.196 Hom.: 2233

Bravo AF: 0.240

Asia WGS AF: 0.178 AC: 619 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	14
DANN	Benign	0.69

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: rs1288548; hg19: chr4-186299985;