rs747985754

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_016818.3(ABCG1):​c.509C>G​(p.Pro170Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. P170L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

ABCG1
NM_016818.3 missense

Scores

10
7
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.24
Variant links:
Genes affected
ABCG1 (HGNC:73): (ATP binding cassette subfamily G member 1) The 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 intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. It is involved in macrophage cholesterol and phospholipids transport, and may regulate cellular lipid homeostasis in other cell types. Six alternative splice variants have been identified. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.923

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ABCG1NM_016818.3 linkc.509C>G p.Pro170Arg missense_variant Exon 4 of 15 ENST00000398449.8 NP_058198.2 P45844-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABCG1ENST00000398449.8 linkc.509C>G p.Pro170Arg missense_variant Exon 4 of 15 1 NM_016818.3 ENSP00000381467.3 P45844-4
ABCG1ENST00000398437.1 linkc.947C>G p.Pro316Arg missense_variant Exon 5 of 16 1 ENSP00000381464.1 E9PGV9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461596
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727130
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Pathogenic
0.50
D
BayesDel_noAF
Pathogenic
0.48
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.77
.;.;D;.;D;.;D
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.97
D;D;D;D;D;D;D
M_CAP
Pathogenic
0.69
D
MetaRNN
Pathogenic
0.92
D;D;D;D;D;D;D
MetaSVM
Pathogenic
0.94
D
MutationAssessor
Uncertain
2.5
.;.;.;M;M;.;.
PrimateAI
Pathogenic
0.88
D
PROVEAN
Pathogenic
-6.5
D;D;D;D;D;D;D
REVEL
Uncertain
0.52
Sift
Benign
0.056
T;T;D;T;T;T;D
Sift4G
Uncertain
0.053
T;T;D;T;T;T;D
Polyphen
1.0
D;P;.;P;D;P;.
Vest4
0.96
MutPred
0.71
.;.;Loss of catalytic residue at D166 (P = 0.0901);Loss of catalytic residue at D166 (P = 0.0901);Loss of catalytic residue at D166 (P = 0.0901);.;.;
MVP
0.97
MPC
1.4
ClinPred
0.99
D
GERP RS
4.8
Varity_R
0.44
gMVP
0.94

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: chr21-43693517; API