2-168954714-T-C

Variant names:

• chr2-168954714-T-C
• rs853778
• NM_003742.4:c.2343+3250A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003742.4(ABCB11):​c.2343+3250A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 151,476 control chromosomes in the GnomAD database, including 22,022 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 0.54 (22022 hom., cov: 32)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 8 publications found

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]

ABCB11 Gene-Disease associations (from GenCC):

• progressive familial intrahepatic cholestasis type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• benign recurrent intrahepatic cholestasis type 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB11	NM_003742.4	c.2343+3250A>G		intron_variant	Intron 19 of 27	ENST00000650372.1	NP_003733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000650372.1	c.2343+3250A>G		intron_variant	Intron 19 of 27		NM_003742.4	ENSP00000497931.1
ABCB11	ENST00000649448.1	c.660+3250A>G		intron_variant	Intron 5 of 14			ENSP00000497165.1
ABCB11	ENST00000439188.1	n.*813+3250A>G		intron_variant	Intron 6 of 14	2		ENSP00000416058.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81088 AN: 151358 Hom.: 22019 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.536 AC: 81125 AN: 151476 Hom.: 22022 Cov.: 32 AF XY: 0.540 AC XY: 39992 AN XY: 73994

African (AFR) AF: 0.482 AC: 19933 AN: 41388

American (AMR) AF: 0.553 AC: 8408 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2135 AN: 3460

East Asian (EAS) AF: 0.629 AC: 3199 AN: 5086

South Asian (SAS) AF: 0.656 AC: 3161 AN: 4818

European-Finnish (FIN) AF: 0.548 AC: 5770 AN: 10538

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36529 AN: 67680

Other (OTH) AF: 0.544 AC: 1145 AN: 2106

Alfa AF: 0.542 Hom.: 38176

Bravo AF: 0.532

Asia WGS AF: 0.621 AC: 2154 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.73
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs853778; hg19: chr2-169811224;