chr2-43812494-G-A

Variant summary

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

The NM_022436.3(ABCG5):​c.*622C>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 0.24 in 152,472 control chromosomes in the GnomAD database, including 5,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5321 hom., cov: 31)
Exomes 𝑓: 0.13 ( 4 hom. )

Consequence

ABCG5
NM_022436.3 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.134
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 -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 2-43812494-G-A is Benign according to our data. Variant chr2-43812494-G-A is described in ClinVar as [Benign]. Clinvar id is 336024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABCG5NM_022436.3 linkuse as main transcriptc.*622C>T 3_prime_UTR_variant 13/13 ENST00000405322.8 NP_071881.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCG5ENST00000405322.8 linkuse as main transcriptc.*622C>T 3_prime_UTR_variant 13/131 NM_022436.3 ENSP00000384513 P1Q9H222-1

Frequencies

GnomAD3 genomes
AF:
0.240
AC:
36488
AN:
151740
Hom.:
5308
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.402
Gnomad AMI
AF:
0.125
Gnomad AMR
AF:
0.287
Gnomad ASJ
AF:
0.188
Gnomad EAS
AF:
0.150
Gnomad SAS
AF:
0.273
Gnomad FIN
AF:
0.125
Gnomad MID
AF:
0.187
Gnomad NFE
AF:
0.160
Gnomad OTH
AF:
0.220
GnomAD4 exome
AF:
0.128
AC:
79
AN:
616
Hom.:
4
Cov.:
0
AF XY:
0.134
AC XY:
48
AN XY:
358
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.202
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.154
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.116
Gnomad4 OTH exome
AF:
0.136
GnomAD4 genome
AF:
0.241
AC:
36534
AN:
151856
Hom.:
5321
Cov.:
31
AF XY:
0.240
AC XY:
17804
AN XY:
74202
show subpopulations
Gnomad4 AFR
AF:
0.402
Gnomad4 AMR
AF:
0.288
Gnomad4 ASJ
AF:
0.188
Gnomad4 EAS
AF:
0.149
Gnomad4 SAS
AF:
0.272
Gnomad4 FIN
AF:
0.125
Gnomad4 NFE
AF:
0.160
Gnomad4 OTH
AF:
0.220
Alfa
AF:
0.172
Hom.:
5195
Bravo
AF:
0.260
Asia WGS
AF:
0.214
AC:
747
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Sitosterolemia 1 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
4.1
DANN
Benign
0.69

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: rs4148195; hg19: chr2-44039633; API