rs11568377

Variant names:

• chr2-168996710-G-A
• rs11568377
• NM_003742.4:c.402C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-168996710-G-A
• chr2-168996710-G-C
• chr2-168996710-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_003742.4(ABCB11):​c.402C>T​(p.Ile134Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,560,136 control chromosomes in the GnomAD database, including 1,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (628 hom., cov: 31)
  • Exomes 𝑓: 0.0057 (505 hom.)
• Consequence: ABCB11 NM_003742.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.894
• 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 2-168996710-G-A is Benign according to our data. Variant chr2-168996710-G-A is described in ClinVar as Benign. ClinVar VariationId is 259155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.894 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 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.402C>T	p.Ile134Ile	synonymous	Exon 6 of 28	NP_003733.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB11	ENST00000650372.1	MANE Select	c.402C>T	p.Ile134Ile	synonymous	Exon 6 of 28	ENSP00000497931.1	O95342
	ABCB11	ENST00000858973.1		c.444C>T	p.Ile148Ile	synonymous	Exon 6 of 28	ENSP00000529032.1
	ABCB11	ENST00000858972.1		c.402C>T	p.Ile134Ile	synonymous	Exon 6 of 27	ENSP00000529031.1

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 7529 AN: 151550 Hom.: 622 Cov.: 31

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0205

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0203

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000736

Gnomad OTH AF: 0.0322

GnomAD2 exomes AF: 0.0132 AC: 2581 AN: 196230 AF XY: 0.0107

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.00804

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000497

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000611

Gnomad OTH exome AF: 0.00391

GnomAD4 exome AF: 0.00575 AC: 8097 AN: 1408486 Hom.: 505 Cov.: 29 AF XY: 0.00540 AC XY: 3764 AN XY: 697598

African (AFR) AF: 0.165 AC: 5242 AN: 31862

American (AMR) AF: 0.0103 AC: 405 AN: 39350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24900

East Asian (EAS) AF: 0.000319 AC: 12 AN: 37626

South Asian (SAS) AF: 0.0163 AC: 1272 AN: 77846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51116

Middle Eastern (MID) AF: 0.00800 AC: 45 AN: 5624

European-Non Finnish (NFE) AF: 0.000319 AC: 345 AN: 1082076

Other (OTH) AF: 0.0134 AC: 776 AN: 58086

GnomAD4 genome AF: 0.0498 AC: 7559 AN: 151650 Hom.: 628 Cov.: 31 AF XY: 0.0476 AC XY: 3527 AN XY: 74124

African (AFR) AF: 0.170 AC: 7030 AN: 41322

American (AMR) AF: 0.0204 AC: 310 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000582 AC: 3 AN: 5156

South Asian (SAS) AF: 0.0201 AC: 97 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10496

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000736 AC: 50 AN: 67906

Other (OTH) AF: 0.0319 AC: 67 AN: 2100

Alfa AF: 0.0219 Hom.: 784

Bravo AF: 0.0570

Asia WGS AF: 0.0210 AC: 74 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	2	Progressive familial intrahepatic cholestasis type 2 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	7.8
DANN	Benign	0.59
PhyloP100		0.89
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs11568377; hg19: chr2-169853220;