2-168925971-A-T

Variant names:

• chr2-168925971-A-T
• rs484066
• NM_003742.4:c.3619-1168T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003742.4(ABCB11):​c.3619-1168T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,024 control chromosomes in the GnomAD database, including 26,988 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (26988 hom., cov: 32)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.923
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.673 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB11	NM_003742.4	MANE Select	c.3619-1168T>A		intron	N/A	NP_003733.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB11	ENST00000650372.1	MANE Select	c.3619-1168T>A		intron	N/A	ENSP00000497931.1	O95342
	ABCB11	ENST00000858973.1		c.3661-1168T>A		intron	N/A	ENSP00000529032.1
	ABCB11	ENST00000858972.1		c.3514-1168T>A		intron	N/A	ENSP00000529031.1

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89446 AN: 151906 Hom.: 26983 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.589 AC: 89478 AN: 152024 Hom.: 26988 Cov.: 32 AF XY: 0.593 AC XY: 44068 AN XY: 74320

African (AFR) AF: 0.454 AC: 18800 AN: 41432

American (AMR) AF: 0.647 AC: 9874 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2532 AN: 3466

East Asian (EAS) AF: 0.648 AC: 3354 AN: 5178

South Asian (SAS) AF: 0.693 AC: 3338 AN: 4820

European-Finnish (FIN) AF: 0.616 AC: 6495 AN: 10548

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42882 AN: 67990

Other (OTH) AF: 0.615 AC: 1299 AN: 2112

Alfa AF: 0.608 Hom.: 3555

Bravo AF: 0.587

Asia WGS AF: 0.635 AC: 2208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.084
DANN	Benign	0.54
PhyloP100		-0.92
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: rs484066; hg19: chr2-169782481;