Variant chr21-42271122-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_016818.3(ABCG1):c.339G>A(p.Leu113=) 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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG1	NM_016818.3 linkuse as main transcript	c.339G>A	p.Leu113=	synonymous_variant	3/15	ENST00000398449.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG1	ENST00000398449.8 linkuse as main transcript	c.339G>A	p.Leu113=	synonymous_variant	3/15	1	NM_016818.3	P1	P45844-4

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

GnomAD3 exomes

AF:

0.00985

AC:

2218

AN:

225236

Hom.:

AF XY:

0.00793

AC XY:

972

AN XY:

122502

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 SAS exome

AF:

0.00104

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

Gnomad4 AFR exome

AF:

0.000535

Gnomad4 AMR exome

AF:

0.0413

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0374

Gnomad4 SAS exome

AF:

0.00134

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000455

Gnomad4 OTH exome

AF:

0.00514

GnomAD4 genome

AF:

0.00437

AC:

666

AN:

152344

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

361

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.0178

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0590

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00119

Hom.:

Bravo

AF:

0.00742

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ABCG1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

7.7

DANN

Benign

0.75

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over