2-168927903-C-T

Position:

• chr2-168927903-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003742.4(ABCB11):​c.3412-541G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0686 in 152,156 control chromosomes in the GnomAD database, including 736 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 0.069 (736 hom., cov: 32)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.675

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB11	NM_003742.4	c.3412-541G>A		intron_variant		ENST00000650372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB11	ENST00000650372.1	c.3412-541G>A		intron_variant			NM_003742.4	P1
ABCB11	ENST00000649448.1	c.1789-541G>A		intron_variant
ABCB11	ENST00000439188.1	c.*1882-613G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0685 AC: 10408 AN: 152038 Hom.: 734 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0513

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.0560

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

GnomAD4 genome AF: 0.0686 AC: 10431 AN: 152156 Hom.: 736 Cov.: 32 AF XY: 0.0727 AC XY: 5411 AN XY: 74384

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0804

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0513

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.0587

Alfa AF: 0.0240 Hom.: 276

Bravo AF: 0.0723

Asia WGS AF: 0.176 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.9
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs16856247; hg19: chr2-169784413;