Variant 21-42276889-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_016818.3(ABCG1):c.538-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 1,613,966 control chromosomes in the GnomAD database, including 3,295 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.040 ( 233 hom., cov: 32)

Exomes 𝑓: 0.051 ( 3062 hom. )

Consequence

ABCG1
NM_016818.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002556

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.636

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 21-42276889-C-T is Benign according to our data. Variant chr21-42276889-C-T is described in ClinVar as [Benign]. Clinvar id is 3056609.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.178 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.538-6C>T		splice_region_variant, splice_polypyrimidine_tract_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.538-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_016818.3	P1	P45844-4

Frequencies

GnomAD3 genomes

AF:

0.0404

AC:

6142

AN:

152214

Hom.:

232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00854

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0433

Gnomad ASJ

AF:

0.0692

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.0266

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0444

Gnomad OTH

AF:

0.0421

GnomAD3 exomes

AF:

0.0643

AC:

16171

AN:

251430

Hom.:

919

AF XY:

0.0709

AC XY:

9633

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.00689

Gnomad AMR exome

AF:

0.0483

Gnomad ASJ exome

AF:

0.0713

Gnomad EAS exome

AF:

0.109

Gnomad SAS exome

AF:

0.177

Gnomad FIN exome

AF:

0.0268

Gnomad NFE exome

AF:

0.0462

Gnomad OTH exome

AF:

0.0668

GnomAD4 exome

AF:

0.0514

AC:

75121

AN:

1461634

Hom.:

3062

Cov.:

AF XY:

0.0556

AC XY:

40391

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.00809

Gnomad4 AMR exome

AF:

0.0469

Gnomad4 ASJ exome

AF:

0.0710

Gnomad4 EAS exome

AF:

0.0858

Gnomad4 SAS exome

AF:

0.172

Gnomad4 FIN exome

AF:

0.0298

Gnomad4 NFE exome

AF:

0.0421

Gnomad4 OTH exome

AF:

0.0598

GnomAD4 genome

AF:

0.0403

AC:

6145

AN:

152332

Hom.:

233

Cov.:

AF XY:

0.0435

AC XY:

3244

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00851

Gnomad4 AMR

AF:

0.0432

Gnomad4 ASJ

AF:

0.0692

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.188

Gnomad4 FIN

AF:

0.0266

Gnomad4 NFE

AF:

0.0444

Gnomad4 OTH

AF:

0.0412

Alfa

AF:

0.0440

Hom.:

Bravo

AF:

0.0381

Asia WGS

AF:

0.114

AC:

395

AN:

3478

EpiCase

AF:

0.0516

EpiControl

AF:

0.0543

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

Jul 12, 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

-0.47

CADD

Benign

9.1

DANN

Uncertain

0.98

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00026

dbscSNV1_RF

Benign

0.022

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