dbSNP rs2229411: ABCG1:p.Leu113Leu (chr21-42271122-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_016818.3(ABCG1):c.339G>A(p.Leu113Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,584,138 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0044 ( 17 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 104 hom. )

Consequence

ABCG1
NM_016818.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.22

Publications

7 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 21-42271122-G-A is Benign according to our data. Variant chr21-42271122-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060995.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016818.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCG1	NM_016818.3	MANE Select	c.339G>A	p.Leu113Leu	synonymous	Exon 3 of 15	NP_058198.2
ABCG1	NM_004915.4		c.339G>A	p.Leu113Leu	synonymous	Exon 3 of 15	NP_004906.3
ABCG1	NM_207174.1		c.372G>A	p.Leu124Leu	synonymous	Exon 3 of 15	NP_997057.1	P45844-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCG1	ENST00000398449.8	TSL:1 MANE Select	c.339G>A	p.Leu113Leu	synonymous	Exon 3 of 15	ENSP00000381467.3	P45844-4
ABCG1	ENST00000398437.1	TSL:1	c.777G>A	p.Leu259Leu	synonymous	Exon 4 of 16	ENSP00000381464.1	E9PGV9
ABCG1	ENST00000361802.7	TSL:1	c.339G>A	p.Leu113Leu	synonymous	Exon 3 of 15	ENSP00000354995.2	P45844-1

Frequencies

GnomAD3 genomes

AF:

0.00439

AC:

669

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0179

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0594

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00985

AC:

2218

AN:

225236

AF XY:

0.00793

show subpopulations

Gnomad AFR exome

AF:

0.000957

Gnomad AMR exome

AF:

0.0482

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0533

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000568

Gnomad OTH exome

AF:

0.00382

GnomAD4 exome

AF:

0.00241

AC:

3449

AN:

1431794

Hom.:

104

Cov.:

AF XY:

0.00212

AC XY:

1507

AN XY:

711886

show subpopulations

African (AFR)

AF:

0.000535

AC:

AN:

31804

American (AMR)

AF:

0.0413

AC:

1599

AN:

38758

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25526

East Asian (EAS)

AF:

0.0374

AC:

1367

AN:

36582

South Asian (SAS)

AF:

0.00134

AC:

109

AN:

81492

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53102

Middle Eastern (MID)

AF:

0.000525

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

0.0000455

AC:

AN:

1099698

Other (OTH)

AF:

0.00514

AC:

304

AN:

59122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

143

285

428

570

713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<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

AF:

0.00437

AC:

666

AN:

152344

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

361

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

41580

American (AMR)

AF:

0.0178

AC:

273

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0590

AC:

306

AN:

5186

South Asian (SAS)

AF:

0.00248

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68036

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

101

135

169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00151

Hom.:

Bravo

AF:

0.00742

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ABCG1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

7.7

(source)

DANN

Benign

0.75

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over