rs12271907

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022169.5(ABCG4):​c.1035C>A​(p.Asn345Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ABCG4
NM_022169.5 missense

Scores

1
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.901
Variant links:
Genes affected
ABCG4 (HGNC:13884): (ATP binding cassette subfamily G member 4) The protein encoded by this gene is a member of the ATP-binding cassette (ABC) transporter superfamily. 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). The encoded protein is a member of the White subfamily and plays an important role in cellular cholesterol homeostasis. This protein functions as either a homodimer or as a heterodimer with another ABC subfamily protein such as ABCG1. [provided by RefSeq, Jan 2017]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04336053).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ABCG4NM_022169.5 linkc.1035C>A p.Asn345Lys missense_variant Exon 9 of 15 ENST00000619701.5 NP_071452.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABCG4ENST00000619701.5 linkc.1035C>A p.Asn345Lys missense_variant Exon 9 of 15 1 NM_022169.5 ENSP00000481728.1 Q9H172-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1460750
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
726686
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:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
0.0040
DANN
Benign
0.84
DEOGEN2
Benign
0.15
T;T;T
Eigen
Benign
-2.1
Eigen_PC
Benign
-2.2
FATHMM_MKL
Benign
0.098
N
LIST_S2
Benign
0.46
.;.;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.043
T;T;T
MetaSVM
Benign
-0.84
T
MutationAssessor
Benign
0.20
N;N;N
PrimateAI
Uncertain
0.51
T
Sift4G
Benign
0.81
T;T;T
Polyphen
0.072
B;B;B
Vest4
0.030
MutPred
0.45
Gain of ubiquitination at N345 (P = 0.0082);Gain of ubiquitination at N345 (P = 0.0082);Gain of ubiquitination at N345 (P = 0.0082);
MVP
0.32
ClinPred
0.082
T
GERP RS
-11
Varity_R
0.047
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.17
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: rs12271907; hg19: chr11-119027691; API