chr2-168923386-T-C

Variant summary

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

The NM_003742.4(ABCB11):​c.*236A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 570,900 control chromosomes in the GnomAD database, including 112,586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 30228 hom., cov: 30)
Exomes 𝑓: 0.62 ( 82358 hom. )

Consequence

ABCB11
NM_003742.4 3_prime_UTR

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.225
Variant links:
Genes affected
ABCB11 (HGNC:42): (ATP binding cassette subfamily B member 11) The membrane-associated 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 MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is the major canalicular bile salt export pump in man. Mutations in this gene cause a form of progressive familial intrahepatic cholestases which are a group of inherited disorders with severe cholestatic liver disease from early infancy. [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=-0.9).
BP6
Variant 2-168923386-T-C is Benign according to our data. Variant chr2-168923386-T-C is described in ClinVar as [Benign]. Clinvar id is 332018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABCB11NM_003742.4 linkuse as main transcriptc.*236A>G 3_prime_UTR_variant 28/28 ENST00000650372.1
ABCB11XM_011512078.3 linkuse as main transcriptc.*190A>G 3_prime_UTR_variant 29/29
ABCB11XM_017005165.2 linkuse as main transcriptc.3867+1271A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABCB11ENST00000650372.1 linkuse as main transcriptc.*236A>G 3_prime_UTR_variant 28/28 NM_003742.4 P1
ABCB11ENST00000649448.1 linkuse as main transcriptc.*236A>G 3_prime_UTR_variant 15/15
ABCB11ENST00000648875.1 linkuse as main transcriptc.226+1271A>G intron_variant
ABCB11ENST00000439188.1 linkuse as main transcriptc.*2600A>G 3_prime_UTR_variant, NMD_transcript_variant 15/152

Frequencies

GnomAD3 genomes
AF:
0.624
AC:
94766
AN:
151856
Hom.:
30197
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.681
Gnomad AMI
AF:
0.761
Gnomad AMR
AF:
0.629
Gnomad ASJ
AF:
0.651
Gnomad EAS
AF:
0.927
Gnomad SAS
AF:
0.772
Gnomad FIN
AF:
0.611
Gnomad MID
AF:
0.604
Gnomad NFE
AF:
0.554
Gnomad OTH
AF:
0.619
GnomAD4 exome
AF:
0.616
AC:
257905
AN:
418926
Hom.:
82358
Cov.:
4
AF XY:
0.623
AC XY:
137126
AN XY:
220164
show subpopulations
Gnomad4 AFR exome
AF:
0.683
Gnomad4 AMR exome
AF:
0.648
Gnomad4 ASJ exome
AF:
0.656
Gnomad4 EAS exome
AF:
0.940
Gnomad4 SAS exome
AF:
0.764
Gnomad4 FIN exome
AF:
0.598
Gnomad4 NFE exome
AF:
0.550
Gnomad4 OTH exome
AF:
0.616
GnomAD4 genome
AF:
0.624
AC:
94858
AN:
151974
Hom.:
30228
Cov.:
30
AF XY:
0.633
AC XY:
47025
AN XY:
74282
show subpopulations
Gnomad4 AFR
AF:
0.681
Gnomad4 AMR
AF:
0.629
Gnomad4 ASJ
AF:
0.651
Gnomad4 EAS
AF:
0.927
Gnomad4 SAS
AF:
0.771
Gnomad4 FIN
AF:
0.611
Gnomad4 NFE
AF:
0.554
Gnomad4 OTH
AF:
0.616
Alfa
AF:
0.568
Hom.:
41434
Bravo
AF:
0.624
Asia WGS
AF:
0.803
AC:
2792
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 29, 2018- -
Progressive familial intrahepatic cholestasis type 2 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
2.7
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: rs473351; hg19: chr2-169779896; API