rs11568371

Variant names:

• chr2-168970063-C-A
• rs11568371
• NM_003742.4:c.1791G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-168970063-C-A
• chr2-168970063-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003742.4(ABCB11):​c.1791G>T​(p.Val597Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00669 in 1,610,312 control chromosomes in the GnomAD database, including 639 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V597V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0050 (45 hom., cov: 32)
  • Exomes 𝑓: 0.0069 (594 hom.)
• Consequence: ABCB11 NM_003742.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -4.18
• Publications: 4 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 2-168970063-C-A is Benign according to our data. Variant chr2-168970063-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 194504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.18 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003742.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB11	NM_003742.4	MANE Select	c.1791G>T	p.Val597Val	synonymous	Exon 15 of 28	NP_003733.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB11	ENST00000650372.1	MANE Select	c.1791G>T	p.Val597Val	synonymous	Exon 15 of 28	ENSP00000497931.1	O95342
	ABCB11	ENST00000858973.1		c.1833G>T	p.Val611Val	synonymous	Exon 15 of 28	ENSP00000529032.1
	ABCB11	ENST00000858972.1		c.1791G>T	p.Val597Val	synonymous	Exon 15 of 27	ENSP00000529031.1

Frequencies

GnomAD3 genomes AF: 0.00498 AC: 756 AN: 151852 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.00401

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000920

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00117

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.0142 AC: 3531 AN: 248574 AF XY: 0.0194

Gnomad AFR exome AF: 0.00375

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00122

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000160

Gnomad OTH exome AF: 0.00547

GnomAD4 exome AF: 0.00687 AC: 10021 AN: 1458342 Hom.: 594 Cov.: 33 AF XY: 0.0101 AC XY: 7294 AN XY: 725520

African (AFR) AF: 0.00390 AC: 130 AN: 33342

American (AMR) AF: 0.000269 AC: 12 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26008

East Asian (EAS) AF: 0.000531 AC: 21 AN: 39556

South Asian (SAS) AF: 0.108 AC: 9297 AN: 86192

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52878

Middle Eastern (MID) AF: 0.00407 AC: 23 AN: 5648

European-Non Finnish (NFE) AF: 0.000106 AC: 118 AN: 1109942

Other (OTH) AF: 0.00697 AC: 419 AN: 60148

GnomAD4 genome AF: 0.00497 AC: 755 AN: 151970 Hom.: 45 Cov.: 32 AF XY: 0.00681 AC XY: 506 AN XY: 74280

African (AFR) AF: 0.00405 AC: 168 AN: 41496

American (AMR) AF: 0.000919 AC: 14 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00117 AC: 6 AN: 5110

South Asian (SAS) AF: 0.115 AC: 554 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67928

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00353 Hom.: 53

Bravo AF: 0.00207

Asia WGS AF: 0.0320 AC: 110 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Progressive familial intrahepatic cholestasis type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.17
DANN	Benign	0.52
PhyloP100		-4.2
PromoterAI		-0.067	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11568371; hg19: chr2-169826573;