rs1048329

Positions:

• chr4-185378604-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.-418C>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 0.202 in 992,950 control chromosomes in the GnomAD database, including 21,128 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 0.23 (4458 hom., cov: 32)
  • Exomes 𝑓: 0.20 (16670 hom.)
• Consequence: LRP2BP NM_018409.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263

Genes affected

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

SNX25 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP2BP	NM_001377440.1	c.-21-397C>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.-21-397C>T		intron_variant		2	NM_001377440.1	ENSP00000426203.1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34978 AN: 151976 Hom.: 4450 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.197 AC: 165756 AN: 840856 Hom.: 16670 Cov.: 31 AF XY: 0.198 AC XY: 76858 AN XY: 388712

Gnomad4 AFR exome AF: 0.341

Gnomad4 AMR exome AF: 0.330

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.201

GnomAD4 genome AF: 0.230 AC: 35009 AN: 152094 Hom.: 4458 Cov.: 32 AF XY: 0.229 AC XY: 17039 AN XY: 74372

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.219

Alfa AF: 0.207 Hom.: 2940

Bravo AF: 0.253

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.32
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1048329; hg19: chr4-186299758;