4-185374404-G-T

Position:

• chr4-185374404-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001377440.1(LRP2BP):​c.388C>A​(p.His130Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LRP2BP NM_001377440.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72

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:55998): (LRP2BP antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21907896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP2BP	NM_001377440.1	c.388C>A	p.His130Asn	missense_variant	5/9	ENST00000505916.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP2BP	ENST00000505916.6	c.388C>A	p.His130Asn	missense_variant	5/9	2	NM_001377440.1	P1
LRP2BP-AS1	ENST00000514884.1	n.242+3339G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2023

The c.388C>A (p.H130N) alteration is located in exon 4 (coding exon 4) of the LRP2BP gene. This alteration results from a C to A substitution at nucleotide position 388, causing the histidine (H) at amino acid position 130 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;.;T;.
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;.;N;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.8	D;D;D;N
REVEL	Benign	0.14
Sift	Benign	0.11	T;T;T;T
Sift4G	Benign	0.27	T;T;T;.
Polyphen		0.68	P;P;P;.
Vest4		0.44
MutPred		0.34		Loss of glycosylation at P126 (P = 0.0432);.;Loss of glycosylation at P126 (P = 0.0432);Loss of glycosylation at P126 (P = 0.0432);
MVP		0.60
MPC		0.25
ClinPred		0.82	D
GERP RS		5.6
Varity_R		0.30
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-186295558;