2-168954714-T-C

Position:

• chr2-168954714-T-C

Variant summary

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

The NM_003742.4(ABCB11):​c.2343+3250A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 151,476 control chromosomes in the GnomAD database, including 22,022 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 0.54 (22022 hom., cov: 32)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203

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 (SAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB11	NM_003742.4	c.2343+3250A>G		intron_variant		ENST00000650372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB11	ENST00000650372.1	c.2343+3250A>G		intron_variant			NM_003742.4	P1
ABCB11	ENST00000649448.1	c.660+3250A>G		intron_variant
ABCB11	ENST00000439188.1	c.*813+3250A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81088 AN: 151358 Hom.: 22019 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.536 AC: 81125 AN: 151476 Hom.: 22022 Cov.: 32 AF XY: 0.540 AC XY: 39992 AN XY: 73994

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.544

Alfa AF: 0.545 Hom.: 30552

Bravo AF: 0.532

Asia WGS AF: 0.621 AC: 2154 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.73

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: rs853778; hg19: chr2-169811224;