rs7605199

Variant names:

• chr2-168999944-A-G
• rs7605199
• NM_003742.4:c.390-3222T>C

Variant summary

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

The NM_003742.4(ABCB11):​c.390-3222T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,898 control chromosomes in the GnomAD database, including 13,347 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 0.41 (13347 hom., cov: 32)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.493 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.390-3222T>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.390-3222T>C		intron	N/A	ENSP00000497931.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62633 AN: 151780 Hom.: 13350 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.412 AC: 62641 AN: 151898 Hom.: 13347 Cov.: 32 AF XY: 0.414 AC XY: 30733 AN XY: 74240

African (AFR) AF: 0.353 AC: 14617 AN: 41430

American (AMR) AF: 0.312 AC: 4760 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1642 AN: 3472

East Asian (EAS) AF: 0.244 AC: 1261 AN: 5172

South Asian (SAS) AF: 0.510 AC: 2459 AN: 4824

European-Finnish (FIN) AF: 0.488 AC: 5146 AN: 10540

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31302 AN: 67908

Other (OTH) AF: 0.397 AC: 836 AN: 2108

Alfa AF: 0.446 Hom.: 25682

Bravo AF: 0.393

Asia WGS AF: 0.371 AC: 1291 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.2
DANN	Benign	0.66
PhyloP100		0.16
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: rs7605199; hg19: chr2-169856454;