chr2-168942500-A-G

Position:

• chr2-168942500-A-G

Variant summary

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

The NM_003742.4(ABCB11):​c.2610+2105T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 60,424 control chromosomes in the GnomAD database, including 3,024 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 0.49 (3024 hom., cov: 30)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB11	NM_003742.4	c.2610+2105T>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.2610+2105T>C		intron_variant			NM_003742.4	ENSP00000497931	P1
ABCB11	ENST00000649448.1	c.927+2105T>C		intron_variant				ENSP00000497165
ABCB11	ENST00000439188.1	c.*1080+2105T>C		intron_variant, NMD_transcript_variant		2		ENSP00000416058

Frequencies

GnomAD3 genomes AF: 0.486 AC: 29354 AN: 60376 Hom.: 3025 Cov.: 30

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.556

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.486 AC: 29356 AN: 60424 Hom.: 3024 Cov.: 30 AF XY: 0.484 AC XY: 13837 AN XY: 28584

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.524

Alfa AF: 0.214 Hom.: 1556

Bravo AF: 0.195

Asia WGS AF: 0.121 AC: 402 AN: 3306

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.4
DANN	Benign	0.50

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: rs6709087; hg19: chr2-169799010;