rs1048329

Variant names:

• chr4-185378604-G-A
• rs1048329
• ENST00000328559.11:c.-418C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

Genes affected

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

SNX25 (HGNC:21883): (sorting nexin 25) Predicted to enable type I transforming growth factor beta receptor binding activity. Involved in negative regulation of pathway-restricted SMAD protein phosphorylation; negative regulation of transforming growth factor beta receptor signaling pathway; and receptor catabolic process. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018409.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP2BP	NM_001377440.1	MANE Select	c.-21-397C>T		intron	N/A	NP_001364369.1	Q9P2M1-1
	LRP2BP	NM_018409.4		c.-418C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_060879.2
	LRP2BP	NM_018409.4		c.-418C>T		5_prime_UTR	Exon 1 of 8	NP_060879.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP2BP	ENST00000328559.11	TSL:1	c.-418C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000332681.7	Q9P2M1-1
	LRP2BP	ENST00000510776.5	TSL:1	c.-1558C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000424610.1	G5E9Z9
	LRP2BP	ENST00000328559.11	TSL:1	c.-418C>T		5_prime_UTR	Exon 1 of 8	ENSP00000332681.7	Q9P2M1-1

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

African (AFR) AF: 0.341 AC: 5482 AN: 16074

American (AMR) AF: 0.330 AC: 490 AN: 1486

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 1148 AN: 5444

East Asian (EAS) AF: 0.183 AC: 710 AN: 3888

South Asian (SAS) AF: 0.152 AC: 2532 AN: 16626

European-Finnish (FIN) AF: 0.162 AC: 86 AN: 532

Middle Eastern (MID) AF: 0.240 AC: 393 AN: 1636

European-Non Finnish (NFE) AF: 0.195 AC: 149332 AN: 767360

Other (OTH) AF: 0.201 AC: 5583 AN: 27810

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

African (AFR) AF: 0.325 AC: 13456 AN: 41450

American (AMR) AF: 0.285 AC: 4352 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 697 AN: 3472

East Asian (EAS) AF: 0.188 AC: 973 AN: 5184

South Asian (SAS) AF: 0.148 AC: 713 AN: 4824

European-Finnish (FIN) AF: 0.133 AC: 1407 AN: 10592

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12760 AN: 67982

Other (OTH) AF: 0.219 AC: 463 AN: 2114

Alfa AF: 0.207 Hom.: 4507

Bravo AF: 0.253

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.32
DANN	Benign	0.68
PhyloP100		-0.26
PromoterAI		0.015	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1048329; hg19: chr4-186299758;