2-168934928-A-G

Variant names:

• chr2-168934928-A-G
• rs552976
• NM_003742.4:c.3056+256T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003742.4(ABCB11):​c.3056+256T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,954 control chromosomes in the GnomAD database, including 33,898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (33898 hom., cov: 31)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.579
• Publications: 45 publications found

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 Gene-Disease associations (from GenCC):

• progressive familial intrahepatic cholestasis type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• benign recurrent intrahepatic cholestasis type 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-168934928-A-G is Benign according to our data. Variant chr2-168934928-A-G is described in ClinVar as Benign. ClinVar VariationId is 1254081.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003742.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB11	NM_003742.4	MANE Select	c.3056+256T>C		intron	N/A	NP_003733.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB11	ENST00000650372.1	MANE Select	c.3056+256T>C		intron	N/A	ENSP00000497931.1
	ABCB11	ENST00000649448.1		c.1373+256T>C		intron	N/A	ENSP00000497165.1
	ABCB11	ENST00000439188.1	TSL:2	n.*1526+256T>C		intron	N/A	ENSP00000416058.1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100545 AN: 151836 Hom.: 33877 Cov.: 31

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.676

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.662 AC: 100613 AN: 151954 Hom.: 33898 Cov.: 31 AF XY: 0.671 AC XY: 49819 AN XY: 74264

African (AFR) AF: 0.586 AC: 24256 AN: 41408

American (AMR) AF: 0.742 AC: 11335 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2614 AN: 3472

East Asian (EAS) AF: 0.987 AC: 5099 AN: 5166

South Asian (SAS) AF: 0.813 AC: 3905 AN: 4806

European-Finnish (FIN) AF: 0.668 AC: 7064 AN: 10568

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.648 AC: 44009 AN: 67944

Other (OTH) AF: 0.674 AC: 1423 AN: 2110

Alfa AF: 0.661 Hom.: 135447

Bravo AF: 0.665

Asia WGS AF: 0.846 AC: 2939 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.4
DANN	Benign	0.70
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs552976; hg19: chr2-169791438;