2-168943763-A-ACGTG

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB11	NM_003742.4	c.2610+841_2610+842insCACG		intron_variant		ENST00000650372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB11	ENST00000650372.1	c.2610+841_2610+842insCACG		intron_variant			NM_003742.4	P1
ABCB11	ENST00000649448.1	c.927+841_927+842insCACG		intron_variant
ABCB11	ENST00000439188.1	c.*1080+841_*1080+842insCACG		intron_variant, NMD_transcript_variant		2

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

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.520

Alfa AF: 0.325 Hom.: 688

Bravo AF: 0.491

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2307959; hg19: chr2-169800273;