rs853773

Positions:

• chr2-168957837-A-G
• chr2-168957837-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003742.4(ABCB11):​c.2343+127T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 986,868 control chromosomes in the GnomAD database, including 148,948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24209 hom., cov: 31)
  • Exomes 𝑓: 0.55 (124739 hom.)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.131

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 2-168957837-A-G is Benign according to our data. Variant chr2-168957837-A-G is described in ClinVar as [Benign]. Clinvar id is 1294312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB11	NM_003742.4	c.2343+127T>C		intron_variant		ENST00000650372.1	NP_003733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000650372.1	c.2343+127T>C		intron_variant			NM_003742.4	ENSP00000497931.1
ABCB11	ENST00000649448.1	c.660+127T>C		intron_variant				ENSP00000497165.1
ABCB11	ENST00000439188.1	n.*813+127T>C		intron_variant		2		ENSP00000416058.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85261 AN: 151254 Hom.: 24197 Cov.: 31

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.564

GnomAD4 exome AF: 0.545 AC: 455517 AN: 835496 Hom.: 124739 AF XY: 0.545 AC XY: 220899 AN XY: 405406

Gnomad4 AFR exome AF: 0.626

Gnomad4 AMR exome AF: 0.585

Gnomad4 ASJ exome AF: 0.626

Gnomad4 EAS exome AF: 0.619

Gnomad4 SAS exome AF: 0.605

Gnomad4 FIN exome AF: 0.519

Gnomad4 NFE exome AF: 0.535

Gnomad4 OTH exome AF: 0.567

GnomAD4 genome AF: 0.564 AC: 85325 AN: 151372 Hom.: 24209 Cov.: 31 AF XY: 0.565 AC XY: 41808 AN XY: 73932

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.561

Alfa AF: 0.519 Hom.: 8825

Bravo AF: 0.569

Asia WGS AF: 0.638 AC: 2217 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.8
DANN	Benign	0.59

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: rs853773; hg19: chr2-169814347;