chr2-168923202-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.*420A>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 0.486 in 175,774 control chromosomes in the GnomAD database, including 22,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18879 hom., cov: 32)
Exomes 𝑓: 0.50 ( 3236 hom. )

Consequence

ABCB11
NM_003742.4 3_prime_UTR

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.236
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=-0.91).
BP6
Variant 2-168923202-T-C is Benign according to our data. Variant chr2-168923202-T-C is described in ClinVar as [Benign]. Clinvar id is 332013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABCB11NM_003742.4 linkuse as main transcriptc.*420A>G 3_prime_UTR_variant 28/28 ENST00000650372.1
ABCB11XM_011512078.3 linkuse as main transcriptc.*374A>G 3_prime_UTR_variant 29/29
ABCB11XM_017005165.2 linkuse as main transcriptc.3867+1455A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABCB11ENST00000650372.1 linkuse as main transcriptc.*420A>G 3_prime_UTR_variant 28/28 NM_003742.4 P1
ABCB11ENST00000649448.1 linkuse as main transcriptc.*420A>G 3_prime_UTR_variant 15/15
ABCB11ENST00000648875.1 linkuse as main transcriptc.226+1455A>G intron_variant

Frequencies

GnomAD3 genomes
AF:
0.483
AC:
73358
AN:
151866
Hom.:
18880
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.303
Gnomad AMI
AF:
0.763
Gnomad AMR
AF:
0.516
Gnomad ASJ
AF:
0.626
Gnomad EAS
AF:
0.625
Gnomad SAS
AF:
0.657
Gnomad FIN
AF:
0.560
Gnomad MID
AF:
0.557
Gnomad NFE
AF:
0.538
Gnomad OTH
AF:
0.512
GnomAD4 exome
AF:
0.505
AC:
12005
AN:
23790
Hom.:
3236
Cov.:
0
AF XY:
0.511
AC XY:
6275
AN XY:
12274
show subpopulations
Gnomad4 AFR exome
AF:
0.249
Gnomad4 AMR exome
AF:
0.544
Gnomad4 ASJ exome
AF:
0.630
Gnomad4 EAS exome
AF:
0.541
Gnomad4 SAS exome
AF:
0.612
Gnomad4 FIN exome
AF:
0.470
Gnomad4 NFE exome
AF:
0.496
Gnomad4 OTH exome
AF:
0.497
GnomAD4 genome
AF:
0.483
AC:
73380
AN:
151984
Hom.:
18879
Cov.:
32
AF XY:
0.490
AC XY:
36396
AN XY:
74282
show subpopulations
Gnomad4 AFR
AF:
0.302
Gnomad4 AMR
AF:
0.517
Gnomad4 ASJ
AF:
0.626
Gnomad4 EAS
AF:
0.625
Gnomad4 SAS
AF:
0.655
Gnomad4 FIN
AF:
0.560
Gnomad4 NFE
AF:
0.538
Gnomad4 OTH
AF:
0.507
Alfa
AF:
0.531
Hom.:
30448
Bravo
AF:
0.470
Asia WGS
AF:
0.605
AC:
2102
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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Progressive familial intrahepatic cholestasis type 2 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
1.9
DANN
Benign
0.30

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: rs496550; hg19: chr2-169779712; COSMIC: COSV55595495; COSMIC: COSV55595495; API