rs1161357167

Variant names:

• chr1-25543708-C-G
• rs1161357167
• NM_015627.3:c.10C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-25543708-C-G
• chr1-25543708-C-T

Variant summary

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

The NM_015627.3(LDLRAP1):​c.10C>G​(p.Leu4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L4F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LDLRAP1 NM_015627.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17

Genes affected

LDLRAP1 (HGNC:18640): (low density lipoprotein receptor adaptor protein 1) The protein encoded by this gene is a cytosolic protein which contains a phosphotyrosine binding (PTD) domain. The PTD domain has been found to interact with the cytoplasmic tail of the LDL receptor. Mutations in this gene lead to LDL receptor malfunction and cause the disorder autosomal recessive hypercholesterolaemia. [provided by RefSeq, Jul 2008]

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 rank	MANE	Protein	UniProt
LDLRAP1	NM_015627.3	c.10C>G	p.Leu4Val	missense_variant	Exon 1 of 9	ENST00000374338.5	NP_056442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDLRAP1	ENST00000374338.5	c.10C>G	p.Leu4Val	missense_variant	Exon 1 of 9	1	NM_015627.3	ENSP00000363458.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.0060	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.99	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.25
MutPred		0.26		Loss of stability (P = 0.067);
MVP		0.73
MPC		0.62
ClinPred		0.98	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.63
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1161357167; hg19: chr1-25870199;