Variant 2-168923182-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_003742.4(ABCB11):c.*440G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 166,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00072 ( 0 hom. )

Consequence

ABCB11
NM_003742.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.529

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]

ABCB11 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 2-168923182-C-T is Benign according to our data. Variant chr2-168923182-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 332012.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ABCB11	NM_003742.4 linkuse as main transcript	c.*440G>A	3_prime_UTR_variant	28/28	ENST00000650372.1
ABCB11	XM_011512078.3 linkuse as main transcript	c.*394G>A	3_prime_UTR_variant	29/29
ABCB11	XM_017005165.2 linkuse as main transcript	c.3867+1475G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Appris
ABCB11	ENST00000650372.1 linkuse as main transcript	c.*440G>A	3_prime_UTR_variant	28/28	NM_003742.4	P1
ABCB11	ENST00000649448.1 linkuse as main transcript	c.*440G>A	3_prime_UTR_variant	15/15
ABCB11	ENST00000648875.1 linkuse as main transcript	c.226+1475G>A	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

179

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.000959

GnomAD4 exome

AF:

0.000720

AC:

AN:

13886

Hom.:

Cov.:

AF XY:

0.000822

AC XY:

AN XY:

7302

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000539

Gnomad4 ASJ exome

AF:

0.00313

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00207

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000703

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00117

AC:

178

AN:

152236

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00159

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000877

Hom.:

Bravo

AF:

0.00133

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Progressive familial intrahepatic cholestasis type 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.0

DANN

Benign

0.60

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