rs11568378

chr2-168996619-C-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.477+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,408,792 control chromosomes in the GnomAD database, including 1,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (626 hom., cov: 31)
  • Exomes 𝑓: 0.0056 (435 hom.)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.31

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=-0.92).
• BP6: Variant 2-168996619-C-T is Benign according to our data. Variant chr2-168996619-C-T is described in ClinVar as [Benign]. Clinvar id is 259156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB11	NM_003742.4	c.477+16G>A		intron_variant		ENST00000650372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB11	ENST00000650372.1	c.477+16G>A		intron_variant			NM_003742.4	P1

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 7544 AN: 151704 Hom.: 620 Cov.: 31

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0205

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000839

Gnomad OTH AF: 0.0331

GnomAD3 exomes AF: 0.0117 AC: 1708 AN: 145666 Hom.: 104 AF XY: 0.00960 AC XY: 751 AN XY: 78214

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.00764

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000729

Gnomad SAS exome AF: 0.0162

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000719

Gnomad OTH exome AF: 0.00422

GnomAD4 exome AF: 0.00561 AC: 7053 AN: 1256970 Hom.: 435 Cov.: 19 AF XY: 0.00528 AC XY: 3278 AN XY: 621412

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000312

Gnomad4 SAS exome AF: 0.0158

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000475

Gnomad4 OTH exome AF: 0.0138

GnomAD4 genome AF: 0.0499 AC: 7577 AN: 151822 Hom.: 626 Cov.: 31 AF XY: 0.0477 AC XY: 3541 AN XY: 74234

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.0205

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0199

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000839

Gnomad4 OTH AF: 0.0328

Alfa AF: 0.0121 Hom.: 158

Bravo AF: 0.0571

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 22, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.010
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11568378; hg19: chr2-169853129; COSMIC: COSV104379524;