rs2287618

Variant names:

• chr2-168986299-T-C
• rs2287618
• NM_003742.4:c.909-15A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003742.4(ABCB11):​c.909-15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 1,607,150 control chromosomes in the GnomAD database, including 397,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (40774 hom., cov: 32)
  • Exomes 𝑓: 0.70 (357173 hom.)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.61
• Publications: 13 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-168986299-T-C is Benign according to our data. Variant chr2-168986299-T-C is described in ClinVar as Benign. ClinVar VariationId is 259158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 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.909-15A>G		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.909-15A>G		intron	N/A	ENSP00000497931.1	O95342
	ABCB11	ENST00000858973.1		c.951-15A>G		intron	N/A	ENSP00000529032.1
	ABCB11	ENST00000858972.1		c.909-15A>G		intron	N/A	ENSP00000529031.1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110510 AN: 151934 Hom.: 40732 Cov.: 32

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.726

GnomAD2 exomes AF: 0.695 AC: 172088 AN: 247692 AF XY: 0.702

Gnomad AFR exome AF: 0.828

Gnomad AMR exome AF: 0.502

Gnomad ASJ exome AF: 0.713

Gnomad EAS exome AF: 0.810

Gnomad FIN exome AF: 0.711

Gnomad NFE exome AF: 0.694

Gnomad OTH exome AF: 0.681

GnomAD4 exome AF: 0.698 AC: 1016246 AN: 1455098 Hom.: 357173 Cov.: 33 AF XY: 0.700 AC XY: 507241 AN XY: 724132

African (AFR) AF: 0.836 AC: 27728 AN: 33164

American (AMR) AF: 0.507 AC: 22589 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 18780 AN: 26056

East Asian (EAS) AF: 0.805 AC: 31896 AN: 39644

South Asian (SAS) AF: 0.758 AC: 65149 AN: 85990

European-Finnish (FIN) AF: 0.699 AC: 37248 AN: 53258

Middle Eastern (MID) AF: 0.686 AC: 3152 AN: 4594

European-Non Finnish (NFE) AF: 0.692 AC: 767010 AN: 1107794

Other (OTH) AF: 0.711 AC: 42694 AN: 60038

GnomAD4 genome AF: 0.727 AC: 110613 AN: 152052 Hom.: 40774 Cov.: 32 AF XY: 0.727 AC XY: 54031 AN XY: 74316

African (AFR) AF: 0.830 AC: 34428 AN: 41498

American (AMR) AF: 0.582 AC: 8882 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2512 AN: 3468

East Asian (EAS) AF: 0.811 AC: 4184 AN: 5160

South Asian (SAS) AF: 0.766 AC: 3690 AN: 4816

European-Finnish (FIN) AF: 0.717 AC: 7576 AN: 10564

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.691 AC: 46989 AN: 67980

Other (OTH) AF: 0.730 AC: 1541 AN: 2112

Alfa AF: 0.698 Hom.: 68834

Bravo AF: 0.720

Asia WGS AF: 0.823 AC: 2864 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	2	Progressive familial intrahepatic cholestasis type 2 (2)
-	-	1	Benign recurrent intrahepatic cholestasis type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.033
DANN	Benign	0.31
PhyloP100		-1.6
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: rs2287618; hg19: chr2-169842809;