4-185372960-G-C

Position:

• chr4-185372960-G-C

Variant summary

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

The NM_001377440.1(LRP2BP):​c.699C>G​(p.Cys233Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRP2BP NM_001377440.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.99

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.699C>G	p.Cys233Trp	missense_variant	7/9	ENST00000505916.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP2BP	ENST00000505916.6	c.699C>G	p.Cys233Trp	missense_variant	7/9	2	NM_001377440.1	P1
LRP2BP	ENST00000328559.11	c.699C>G	p.Cys233Trp	missense_variant	6/8	1		P1
LRP2BP	ENST00000510776.5	c.621C>G	p.Cys207Trp	missense_variant	5/7	1
LRP2BP-AS1	ENST00000514884.1	n.242+1895G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jun 14, 2023

The c.699C>G (p.C233W) alteration is located in exon 6 (coding exon 6) of the LRP2BP gene. This alteration results from a C to G substitution at nucleotide position 699, causing the cysteine (C) at amino acid position 233 to be replaced by a tryptophan (W). 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	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T;.;T
Eigen	Benign	-0.082
Eigen_PC	Benign	0.042
FATHMM_MKL	Uncertain	0.81	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	-1.3	N;.;N
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.44
MutPred		0.64		Gain of catalytic residue at L231 (P = 0.0055);.;Gain of catalytic residue at L231 (P = 0.0055);
MVP		0.52
MPC		0.90
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.25
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-186294114;