2-43839035-T-G

Position:

chr2-43839035-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000272286.4(ABCG8):c.-19T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,549,390 control chromosomes in the GnomAD database, including 104,532 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11545 hom., cov: 32)

Exomes 𝑓: 0.35 ( 92987 hom. )

Consequence

ABCG8
ENST00000272286.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.65

Variant links:

Genes affected

ABCG8 (HGNC:13887): (ATP binding cassette subfamily G member 8) 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. The protein encoded by this gene functions to exclude non-cholesterol sterol entry at the intestinal level, promote excretion of cholesterol and sterols into bile, and to facilitate transport of sterols back into the intestinal lumen. It is expressed in a tissue-specific manner in the liver, intestine, and gallbladder. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG5. Mutations in this gene may contribute to sterol accumulation and atherosclerosis, and have been observed in patients with sitosterolemia. [provided by RefSeq, Jul 2008]

ABCG8 links:

ABCG5 (HGNC:):

ABCG5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 2-43839035-T-G is Benign according to our data. Variant chr2-43839035-T-G is described in ClinVar as [Benign]. Clinvar id is 193450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-43839035-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
ABCG8	NM_022437.3 linkuse as main transcript	c.-19T>G	5_prime_UTR_variant	1/13	ENST00000272286.4	NP_071882.1
ABCG8	NM_001357321.2 linkuse as main transcript	c.-19T>G	5_prime_UTR_variant	1/13		NP_001344250.1
ABCG5	XM_047445409.1 linkuse as main transcript	c.-289A>C	5_prime_UTR_variant	1/13		XP_047301365.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCG8	ENST00000272286.4 linkuse as main transcript	c.-19T>G	5_prime_UTR_variant	1/13	1	NM_022437.3	ENSP00000272286	P1	Q9H221-1
ABCG8	ENST00000644611.1 linkuse as main transcript	c.76-5472T>G	intron_variant				ENSP00000495423
ABCG8	ENST00000643284.1 linkuse as main transcript	n.521-5472T>G	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.375

AC:

56881

AN:

151856

Hom.:

11520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.405

Gnomad AMI

AF:

0.187

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.845

Gnomad SAS

AF:

0.524

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.352

GnomAD3 exomes

AF:

0.398

AC:

61687

AN:

154852

Hom.:

14051

AF XY:

0.403

AC XY:

33020

AN XY:

82020

show subpopulations

Gnomad AFR exome

AF:

0.400

Gnomad AMR exome

AF:

0.374

Gnomad ASJ exome

AF:

0.230

Gnomad EAS exome

AF:

0.852

Gnomad SAS exome

AF:

0.504

Gnomad FIN exome

AF:

0.369

Gnomad NFE exome

AF:

0.318

Gnomad OTH exome

AF:

0.349

GnomAD4 exome

AF:

0.351

AC:

489991

AN:

1397414

Hom.:

92987

Cov.:

AF XY:

0.355

AC XY:

244563

AN XY:

689280

show subpopulations

Gnomad4 AFR exome

AF:

0.396

Gnomad4 AMR exome

AF:

0.372

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.852

Gnomad4 SAS exome

AF:

0.501

Gnomad4 FIN exome

AF:

0.369

Gnomad4 NFE exome

AF:

0.323

Gnomad4 OTH exome

AF:

0.355

GnomAD4 genome

AF:

0.375

AC:

56943

AN:

151976

Hom.:

11545

Cov.:

AF XY:

0.383

AC XY:

28420

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.405

Gnomad4 AMR

AF:

0.363

Gnomad4 ASJ

AF:

0.245

Gnomad4 EAS

AF:

0.845

Gnomad4 SAS

AF:

0.524

Gnomad4 FIN

AF:

0.372

Gnomad4 NFE

AF:

0.323

Gnomad4 OTH

AF:

0.358

Alfa

AF:

0.247

Hom.:

864

Bravo

AF:

0.371

Asia WGS

AF:

0.606

AC:

2107

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 16, 2015	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 04, 2023	- -

Sitosterolemia 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 14, 2020	- -

Sitosterolemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.77

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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