rs478333

Variant names:

• chr2-168922646-G-A
• rs478333
• NM_003742.4:c.*976C>T

Variant summary

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

The NM_003742.4(ABCB11):​c.*976C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,936 control chromosomes in the GnomAD database, including 18,262 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 0.47 (18262 hom., cov: 31)
• Consequence: ABCB11 NM_003742.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB11	NM_003742.4	c.*976C>T		3_prime_UTR_variant	Exon 28 of 28	ENST00000650372.1	NP_003733.2
ABCB11	XM_017005165.2	c.3867+2011C>T		intron_variant	Intron 27 of 27		XP_016860654.1
ABCB11	XM_011512078.3	c.*930C>T		downstream_gene_variant			XP_011510380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000650372.1	c.*976C>T		3_prime_UTR_variant	Exon 28 of 28		NM_003742.4	ENSP00000497931.1
ABCB11	ENST00000648875.1	c.225+2011C>T		intron_variant	Intron 2 of 2			ENSP00000497252.1

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71376 AN: 151820 Hom.: 18267 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.470 AC: 71379 AN: 151936 Hom.: 18262 Cov.: 31 AF XY: 0.478 AC XY: 35465 AN XY: 74248

African (AFR) AF: 0.262 AC: 10835 AN: 41430

American (AMR) AF: 0.511 AC: 7799 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2125 AN: 3468

East Asian (EAS) AF: 0.636 AC: 3284 AN: 5164

South Asian (SAS) AF: 0.653 AC: 3145 AN: 4814

European-Finnish (FIN) AF: 0.560 AC: 5898 AN: 10526

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.536 AC: 36415 AN: 67958

Other (OTH) AF: 0.487 AC: 1029 AN: 2112

Alfa AF: 0.519 Hom.: 30000

Bravo AF: 0.455

Asia WGS AF: 0.600 AC: 2086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.64
DANN	Benign	0.77
PhyloP100		-0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs478333; hg19: chr2-169779156;