Genetic Variant ABCG1:p.His133Gln (chr21-42259328-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000398437.1(ABCG1):c.399T>G(p.His133Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,396,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 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: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

ABCG1
ENST00000398437.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01

Publications

0 publications found

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]

ABCG1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0829072).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000398437.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ABCG1	NM_016818.3	MANE Select	c.287-11742T>G	intron	N/A	NP_058198.2
ABCG1	NM_004915.4		c.287-11742T>G	intron	N/A	NP_004906.3
ABCG1	NM_207174.1		c.320-11742T>G	intron	N/A	NP_997057.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABCG1	ENST00000398437.1	TSL:1	c.399T>G	p.His133Gln	missense	Exon 2 of 16	ENSP00000381464.1
ABCG1	ENST00000398449.8	TSL:1 MANE Select	c.287-11742T>G		intron	N/A	ENSP00000381467.3
ABCG1	ENST00000361802.7	TSL:1	c.287-11742T>G		intron	N/A	ENSP00000354995.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1396376

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688628

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31530

American (AMR)

AF:

0.00

AC:

AN:

35582

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25070

East Asian (EAS)

AF:

0.00

AC:

AN:

35700

South Asian (SAS)

AF:

0.00

AC:

AN:

78978

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5410

European-Non Finnish (NFE)

AF:

0.00000371

AC:

AN:

1078020

Other (OTH)

AF:

0.00

AC:

AN:

57926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.14

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.23

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0075

LIST_S2

Benign

0.19

M_CAP

Benign

0.039

MetaRNN

Benign

0.083

MetaSVM

Benign

-0.80

PhyloP100

-1.0

PROVEAN

Benign

-0.060

REVEL

Benign

0.17

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.015

Vest4

0.026

MutPred

0.41

Loss of loop (P = 0.0031)

MVP

0.61

ClinPred

0.55

GERP RS

-1.6

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over