rs11568367

Variant names:

• chr2-168970082-T-C
• rs11568367
• NM_003742.4:c.1772A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-168970082-T-C
• chr2-168970082-T-A
• chr2-168970082-T-G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM1 BP4_Strong BP6_Very_Strong BA1

The NM_003742.4(ABCB11):​c.1772A>G​(p.Asn591Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00658 in 1,612,642 control chromosomes in the GnomAD database, including 640 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (45 hom., cov: 32)
  • Exomes 𝑓: 0.0068 (595 hom.)
• Consequence: ABCB11 NM_003742.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 6.27
• Publications: 28 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 -18 ACMG points.

• PM1: In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 5 uncertain in NM_003742.4
• BP4: Computational evidence support a benign effect (MetaRNN=0.0026473403).
• BP6: Variant 2-168970082-T-C is Benign according to our data. Variant chr2-168970082-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 194505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.1772A>G	p.Asn591Ser	missense	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.1772A>G	p.Asn591Ser	missense	Exon 15 of 28	ENSP00000497931.1	O95342
	ABCB11	ENST00000858973.1		c.1814A>G	p.Asn605Ser	missense	Exon 15 of 28	ENSP00000529032.1
	ABCB11	ENST00000858972.1		c.1772A>G	p.Asn591Ser	missense	Exon 15 of 27	ENSP00000529031.1

Frequencies

GnomAD3 genomes AF: 0.00417 AC: 634 AN: 151928 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

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: 0.00192

GnomAD2 exomes AF: 0.0142 AC: 3525 AN: 248634 AF XY: 0.0194

Gnomad AFR exome AF: 0.00168

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00223

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.00530

GnomAD4 exome AF: 0.00683 AC: 9977 AN: 1460596 Hom.: 595 Cov.: 33 AF XY: 0.0100 AC XY: 7291 AN XY: 726614

African (AFR) AF: 0.00162 AC: 54 AN: 33404

American (AMR) AF: 0.000202 AC: 9 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.000958 AC: 38 AN: 39676

South Asian (SAS) AF: 0.108 AC: 9321 AN: 86218

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53396

Middle Eastern (MID) AF: 0.00401 AC: 23 AN: 5740

European-Non Finnish (NFE) AF: 0.000106 AC: 118 AN: 1111120

Other (OTH) AF: 0.00685 AC: 413 AN: 60298

GnomAD4 genome AF: 0.00415 AC: 631 AN: 152046 Hom.: 45 Cov.: 32 AF XY: 0.00612 AC XY: 455 AN XY: 74330

African (AFR) AF: 0.00140 AC: 58 AN: 41526

American (AMR) AF: 0.000197 AC: 3 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00117 AC: 6 AN: 5126

South Asian (SAS) AF: 0.115 AC: 555 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67938

Other (OTH) AF: 0.00190 AC: 4 AN: 2108

Alfa AF: 0.000923 Hom.: 22

Bravo AF: 0.00114

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00102 AC: 4

ESP6500EA AF: 0.000240 AC: 2

ExAC AF: 0.0158 AC: 1909

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
-	-	3	not specified (3)
-	-	3	Progressive familial intrahepatic cholestasis type 2 (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	-0.67	N
PhyloP100		6.3
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.84	N
REVEL	Uncertain	0.29
Sift	Benign	0.14	T
Sift4G	Benign	0.20	T
Polyphen		0.98	D
Vest4		0.69
MPC		0.51
ClinPred		0.017	T
GERP RS		5.2
PromoterAI		-0.036	Neutral
Varity_R		0.17
gMVP		0.52
Mutation Taster		=75/25	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11568367; hg19: chr2-169826592;