2-43812581-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_022436.3(ABCG5):​c.*535C>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 0.0055 in 166,610 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 5 hom., cov: 31)
Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

ABCG5
NM_022436.3 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.694
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]

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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=-0.84).
BP6
Variant 2-43812581-G-A is Benign according to our data. Variant chr2-43812581-G-A is described in ClinVar as [Benign]. Clinvar id is 894906.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00599 (912/152138) while in subpopulation AFR AF= 0.0205 (849/41470). AF 95% confidence interval is 0.0193. There are 5 homozygotes in gnomad4. There are 430 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABCG5NM_022436.3 linkuse as main transcriptc.*535C>T 3_prime_UTR_variant 13/13 ENST00000405322.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABCG5ENST00000405322.8 linkuse as main transcriptc.*535C>T 3_prime_UTR_variant 13/131 NM_022436.3 P1Q9H222-1
ABCG5ENST00000486512.5 linkuse as main transcriptn.3012C>T non_coding_transcript_exon_variant 9/91
ABCG5ENST00000644754.1 linkuse as main transcriptn.2875C>T non_coding_transcript_exon_variant 10/10

Frequencies

GnomAD3 genomes
AF:
0.00601
AC:
914
AN:
152020
Hom.:
5
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0206
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00269
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00766
GnomAD4 exome
AF:
0.000345
AC:
5
AN:
14472
Hom.:
0
Cov.:
0
AF XY:
0.000135
AC XY:
1
AN XY:
7390
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00166
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00147
GnomAD4 genome
AF:
0.00599
AC:
912
AN:
152138
Hom.:
5
Cov.:
31
AF XY:
0.00578
AC XY:
430
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.0205
Gnomad4 AMR
AF:
0.00268
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00758
Alfa
AF:
0.00290
Hom.:
2
Bravo
AF:
0.00700
Asia WGS
AF:
0.000577
AC:
2
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 submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.91
DANN
Benign
0.61

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.

Other links and lift over

dbSNP: rs77638440; hg19: chr2-44039720; API