Variant 2-43812717-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_022436.3(ABCG5):c.*399C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 202,068 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 86 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 2 hom. )

Consequence

ABCG5
NM_022436.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.659

Variant links:

Genes affected

ABCG5 (HGNC:13886): (ATP binding cassette subfamily G member 5) 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 as a half-transporter to limit intestinal absorption and promote biliary excretion of sterols. It is expressed in a tissue-specific manner in the liver, colon, and intestine. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG8. Mutations in this gene may contribute to sterol accumulation and atheroschlerosis, and have been observed in patients with sitosterolemia. [provided by RefSeq, Jul 2008]

ABCG5 links:

DYNC2LI1 (HGNC:):

DYNC2LI1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-43812717-G-A is Benign according to our data. Variant chr2-43812717-G-A is described in ClinVar as [Benign]. Clinvar id is 336030.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG5	NM_022436.3 linkuse as main transcript	c.*399C>T		3_prime_UTR_variant	13/13	ENST00000405322.8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG5	ENST00000405322.8 linkuse as main transcript	c.*399C>T	3_prime_UTR_variant	13/13	1	NM_022436.3	P1	Q9H222-1
ABCG5	ENST00000486512.5 linkuse as main transcript	n.2876C>T	non_coding_transcript_exon_variant	9/9	1
ABCG5	ENST00000644754.1 linkuse as main transcript	n.2739C>T	non_coding_transcript_exon_variant	10/10

Frequencies

GnomAD3 genomes

AF:

0.0182

AC:

2770

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00878

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0177

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0110

GnomAD4 exome

AF:

0.00317

AC:

158

AN:

49920

Hom.:

Cov.:

AF XY:

0.00402

AC XY:

103

AN XY:

25612

show subpopulations

Gnomad4 AFR exome

AF:

0.0522

Gnomad4 AMR exome

AF:

0.00400

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0138

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000198

Gnomad4 OTH exome

AF:

0.00306

GnomAD4 genome

AF:

0.0182

AC:

2772

AN:

152148

Hom.:

Cov.:

AF XY:

0.0181

AC XY:

1347

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0602

Gnomad4 AMR

AF:

0.00876

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0177

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0229

Hom.:

Bravo

AF:

0.0201

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Sitosterolemia 1

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.3

DANN

Benign

0.36

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