2-168943763-A-ACGTG

Variant names:

• chr2-168943763-A-ACGTG
• rs2307959
• NM_003742.4:c.2610+841_2610+842insCACG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_003742.4(ABCB11):​c.2610+841_2610+842insCACG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (19516 hom., cov: 0)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189
• Publications: 6 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.643 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.2610+841_2610+842insCACG		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.2610+841_2610+842insCACG		intron	N/A	ENSP00000497931.1
	ABCB11	ENST00000649448.1		c.927+841_927+842insCACG		intron	N/A	ENSP00000497165.1
	ABCB11	ENST00000439188.1	TSL:2	n.*1080+841_*1080+842insCACG		intron	N/A	ENSP00000416058.1

Frequencies

GnomAD3 genomes AF: 0.495 AC: 74828 AN: 151296 Hom.: 19517 Cov.: 0

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.494 AC: 74845 AN: 151414 Hom.: 19516 Cov.: 0 AF XY: 0.501 AC XY: 37059 AN XY: 73924

African (AFR) AF: 0.323 AC: 13347 AN: 41362

American (AMR) AF: 0.557 AC: 8463 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2140 AN: 3454

East Asian (EAS) AF: 0.625 AC: 3185 AN: 5094

South Asian (SAS) AF: 0.662 AC: 3188 AN: 4814

European-Finnish (FIN) AF: 0.566 AC: 5907 AN: 10436

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36680 AN: 67772

Other (OTH) AF: 0.520 AC: 1088 AN: 2094

Alfa AF: 0.325 Hom.: 688

Bravo AF: 0.491

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2307959; hg19: chr2-169800273;