2-168944587-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2 BP4_Strong BP6_Very_Strong

The NM_003742.4(ABCB11):c.2610+18A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000475 in 1,573,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (0 hom.)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.00800

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 -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-168944587-T-G is Benign according to our data. Variant chr2-168944587-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 259150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB11	NM_003742.4	c.2610+18A>C		intron_variant		ENST00000650372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB11	ENST00000650372.1	c.2610+18A>C		intron_variant			NM_003742.4	P1
ABCB11	ENST00000649448.1	c.927+18A>C		intron_variant
ABCB11	ENST00000439188.1	c.*1080+18A>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000651 AC: 99 AN: 152000 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000795

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000637 AC: 139 AN: 218050 Hom.: 0 AF XY: 0.000592 AC XY: 70 AN XY: 118202

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000369

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000302

Gnomad NFE exome AF: 0.00102

Gnomad OTH exome AF: 0.000772

GnomAD4 exome AF: 0.000457 AC: 649 AN: 1421342 Hom.: 0 Cov.: 31 AF XY: 0.000460 AC XY: 324 AN XY: 703884

Gnomad4 AFR exome AF: 0.0000317

Gnomad4 AMR exome AF: 0.000488

Gnomad4 ASJ exome AF: 0.00198

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000634

Gnomad4 NFE exome AF: 0.000475

Gnomad4 OTH exome AF: 0.000496

GnomAD4 genome AF: 0.000651 AC: 99 AN: 152118 Hom.: 0 Cov.: 32 AF XY: 0.000578 AC XY: 43 AN XY: 74380

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00151

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000795

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000709 Hom.: 0

Bravo AF: 0.000703

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2017	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

Likely 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	-0.89
Cadd	Benign	5.3
Dann	Benign	0.46

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: rs11568374; hg19: chr2-169801097;