rs478333

Positions:

• chr2-168922646-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• 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/exons	MANE	Protein	UniProt
ABCB11	NM_003742.4	c.*976C>T		3_prime_UTR_variant	28/28	ENST00000650372.1	NP_003733.2
ABCB11	XM_017005165.2	c.3867+2011C>T		intron_variant			XP_016860654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000650372.1	c.*976C>T		3_prime_UTR_variant	28/28		NM_003742.4	ENSP00000497931	P1
ABCB11	ENST00000648875.1	c.226+2011C>T		intron_variant				ENSP00000497252

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

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.487

Alfa AF: 0.530 Hom.: 23379

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs478333; hg19: chr2-169779156;