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rs2230806

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005502.4(ABCA1):c.656G>C(p.Arg219Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 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. R219K) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Consequence

ABCA1
NM_005502.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.545
Variant links:
Genes affected
ABCA1 (HGNC:29): (ATP binding cassette subfamily A member 1) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. With cholesterol as its substrate, this protein functions as a cholesteral efflux pump in the cellular lipid removal pathway. Mutations in both alleles of this gene cause Tangier disease and familial high-density lipoprotein (HDL) deficiency. [provided by RefSeq, Sep 2019]

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ACMG classification

Classification made for transcript

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=0.15142757).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABCA1NM_005502.4 linkuse as main transcriptc.656G>C p.Arg219Thr missense_variant 7/50 ENST00000374736.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABCA1ENST00000374736.8 linkuse as main transcriptc.656G>C p.Arg219Thr missense_variant 7/501 NM_005502.4 P1
ABCA1ENST00000678995.1 linkuse as main transcriptc.656G>C p.Arg219Thr missense_variant 7/50
ABCA1ENST00000423487.6 linkuse as main transcriptc.656G>C p.Arg219Thr missense_variant 7/82

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
42
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.097
BayesDel_addAF
Uncertain
0.083
D
BayesDel_noAF
Benign
-0.12
Cadd
Benign
12
Dann
Benign
0.85
DEOGEN2
Benign
0.27
T;T
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.56
FATHMM_MKL
Benign
0.47
N
LIST_S2
Benign
0.72
T;D
M_CAP
Benign
0.066
D
MetaRNN
Benign
0.15
T;T
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Benign
1.0
L;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.59
N;N
REVEL
Benign
0.19
Sift
Benign
0.22
T;T
Sift4G
Benign
0.58
T;T
Polyphen
0.0010
B;.
Vest4
0.29
MutPred
0.39
Gain of phosphorylation at R219 (P = 0.0473);Gain of phosphorylation at R219 (P = 0.0473);
MVP
0.94
MPC
0.26
ClinPred
0.057
T
GERP RS
0.057
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.11
gMVP
0.12

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2230806; hg19: chr9-107620867; API