rs7602204

chr2-168986301-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.909-17G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 1,606,816 control chromosomes in the GnomAD database, including 4,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2247 hom., cov: 32)
  • Exomes 𝑓: 0.027 (2157 hom.)
• Consequence: ABCB11 NM_003742.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.635

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=-0.91).
• BP6: Variant 2-168986301-C-T is Benign according to our data. Variant chr2-168986301-C-T is described in ClinVar as [Benign]. Clinvar id is 259159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-168986301-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB11	NM_003742.4	c.909-17G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000650372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB11	ENST00000650372.1	c.909-17G>A		splice_polypyrimidine_tract_variant, intron_variant			NM_003742.4	P1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15976 AN: 151964 Hom.: 2236 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0215

Gnomad OTH AF: 0.0852

GnomAD3 exomes AF: 0.0391 AC: 9662 AN: 247360 Hom.: 872 AF XY: 0.0346 AC XY: 4640 AN XY: 134190

Gnomad AFR exome AF: 0.327

Gnomad AMR exome AF: 0.0269

Gnomad ASJ exome AF: 0.0257

Gnomad EAS exome AF: 0.000613

Gnomad SAS exome AF: 0.0298

Gnomad FIN exome AF: 0.00343

Gnomad NFE exome AF: 0.0203

Gnomad OTH exome AF: 0.0297

GnomAD4 exome AF: 0.0271 AC: 39372 AN: 1454734 Hom.: 2157 Cov.: 29 AF XY: 0.0262 AC XY: 18963 AN XY: 723928

Gnomad4 AFR exome AF: 0.325

Gnomad4 AMR exome AF: 0.0301

Gnomad4 ASJ exome AF: 0.0267

Gnomad4 EAS exome AF: 0.000328

Gnomad4 SAS exome AF: 0.0299

Gnomad4 FIN exome AF: 0.00393

Gnomad4 NFE exome AF: 0.0192

Gnomad4 OTH exome AF: 0.0389

GnomAD4 genome AF: 0.105 AC: 16024 AN: 152082 Hom.: 2247 Cov.: 32 AF XY: 0.101 AC XY: 7539 AN XY: 74346

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.0514

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0309

Gnomad4 FIN AF: 0.00358

Gnomad4 NFE AF: 0.0215

Gnomad4 OTH AF: 0.0848

Alfa AF: 0.0576 Hom.: 164

Bravo AF: 0.118

Asia WGS AF: 0.0390 AC: 135 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	Jan 27, 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	-0.91
Cadd	Benign	2.2
Dann	Benign	0.49

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: rs7602204; hg19: chr2-169842811;