rs7605199

Variant names:

• chr2-168999944-A-G
• rs7605199
• NM_003742.4:c.390-3222T>C

Variant summary

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

The NM_003742.4(ABCB11):​c.390-3222T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,898 control chromosomes in the GnomAD database, including 13,347 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 0.41 (13347 hom., cov: 32)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB11	NM_003742.4	c.390-3222T>C		intron_variant	Intron 5 of 27	ENST00000650372.1	NP_003733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000650372.1	c.390-3222T>C		intron_variant	Intron 5 of 27		NM_003742.4	ENSP00000497931.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62633 AN: 151780 Hom.: 13350 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.412 AC: 62641 AN: 151898 Hom.: 13347 Cov.: 32 AF XY: 0.414 AC XY: 30733 AN XY: 74240

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.397

Alfa AF: 0.454 Hom.: 20811

Bravo AF: 0.393

Asia WGS AF: 0.371 AC: 1291 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.2
DANN	Benign	0.66

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: rs7605199; hg19: chr2-169856454;