chr4-185375651-C-A

Position:

• chr4-185375651-C-A

Variant summary

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

The NM_001377440.1(LRP2BP):​c.292G>T​(p.Val98Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000664 in 150,708 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 28)
• Consequence: LRP2BP NM_001377440.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.06

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP2BP	NM_001377440.1	c.292G>T	p.Val98Leu	missense_variant	4/9	ENST00000505916.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP2BP	ENST00000505916.6	c.292G>T	p.Val98Leu	missense_variant	4/9	2	NM_001377440.1	P1
LRP2BP-AS1	ENST00000514884.1	n.242+4586C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00000664 AC: 1 AN: 150708 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000661

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000664 AC: 1 AN: 150708 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 73476

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000661

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

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

Feb 02, 2022

The c.292G>T (p.V98L) alteration is located in exon 3 (coding exon 3) of the LRP2BP gene. This alteration results from a G to T substitution at nucleotide position 292, causing the valine (V) at amino acid position 98 to be replaced by a leucine (L). 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	Uncertain	0.54
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T;.;T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.6	M;.;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.1	N;N;N;N
REVEL	Benign	0.21
Sift	Uncertain	0.021	D;D;D;D
Sift4G	Benign	0.21	T;T;T;.
Polyphen		1.0	D;D;D;.
Vest4		0.65
MutPred		0.35		Gain of glycosylation at Y100 (P = 0.0471);.;Gain of glycosylation at Y100 (P = 0.0471);Gain of glycosylation at Y100 (P = 0.0471);
MVP		0.81
MPC		0.64
ClinPred		0.95	D
GERP RS		5.1
Varity_R		0.57
gMVP		0.38

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: rs2095434966; hg19: chr4-186296805;