2-168925971-A-T

Variant names:

• chr2-168925971-A-T
• rs484066
• NM_003742.4:c.3619-1168T>A

Variant summary

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

The NM_003742.4(ABCB11):​c.3619-1168T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,024 control chromosomes in the GnomAD database, including 26,988 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 0.59 (26988 hom., cov: 32)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.923

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB11	NM_003742.4	c.3619-1168T>A		intron_variant	Intron 26 of 27	ENST00000650372.1	NP_003733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000650372.1	c.3619-1168T>A		intron_variant	Intron 26 of 27		NM_003742.4	ENSP00000497931.1
ABCB11	ENST00000649448.1	c.1996-1168T>A		intron_variant	Intron 13 of 14			ENSP00000497165.1
ABCB11	ENST00000648875.1	c.79-1168T>A		intron_variant	Intron 1 of 2			ENSP00000497252.1
ABCB11	ENST00000439188.1	n.*2017-1168T>A		intron_variant	Intron 13 of 14	2		ENSP00000416058.1

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89446 AN: 151906 Hom.: 26983 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.589 AC: 89478 AN: 152024 Hom.: 26988 Cov.: 32 AF XY: 0.593 AC XY: 44068 AN XY: 74320

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.731

Gnomad4 EAS AF: 0.648

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.615

Alfa AF: 0.608 Hom.: 3555

Bravo AF: 0.587

Asia WGS AF: 0.635 AC: 2208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.084
DANN	Benign	0.54

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: rs484066; hg19: chr2-169782481;