Variant chr21-42225918-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_016818.3(ABCG1):c.286+4G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,610,526 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 27 hom. )

Consequence

ABCG1
NM_016818.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.001422

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.06

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=-0.32).

BP6

Variant 21-42225918-G-A is Benign according to our data. Variant chr21-42225918-G-A is described in ClinVar as [Benign]. Clinvar id is 719214.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00153 (2224/1458244) while in subpopulation EAS AF= 0.024 (953/39652). AF 95% confidence interval is 0.0228. There are 27 homozygotes in gnomad4_exome. There are 1104 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG1	NM_016818.3 linkuse as main transcript	c.286+4G>A		splice_donor_region_variant, intron_variant		ENST00000398449.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG1	ENST00000398449.8 linkuse as main transcript	c.286+4G>A		splice_donor_region_variant, intron_variant		1	NM_016818.3	P1	P45844-4

Frequencies

GnomAD3 genomes

AF:

0.00173

AC:

264

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0169

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0126

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00307

AC:

764

AN:

248474

Hom.:

AF XY:

0.00277

AC XY:

374

AN XY:

135014

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.0174

Gnomad SAS exome

AF:

0.00206

Gnomad FIN exome

AF:

0.0123

Gnomad NFE exome

AF:

0.000806

Gnomad OTH exome

AF:

0.00297

GnomAD4 exome

AF:

0.00153

AC:

2224

AN:

1458244

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

1104

AN XY:

725036

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.0240

Gnomad4 SAS exome

AF:

0.00227

Gnomad4 FIN exome

AF:

0.0112

Gnomad4 NFE exome

AF:

0.000315

Gnomad4 OTH exome

AF:

0.00201

GnomAD4 genome

AF:

0.00173

AC:

264

AN:

152282

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

171

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0172

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0126

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000477

Hom.:

Bravo

AF:

0.00104

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 27, 2018

- -

ABCG1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 20, 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

-0.32

CADD

Benign

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0014

dbscSNV1_RF

Benign

0.042

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

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