rs2287622

Variant names:

• chr2-168973818-A-C
• rs2287622
• NM_003742.4:c.1331T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-168973818-A-C
• chr2-168973818-A-G
• chr2-168973818-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003742.4(ABCB11):​c.1331T>G​(p.Val444Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V444A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ABCB11 NM_003742.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.39
• Publications: 164 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36985135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB11	NM_003742.4	c.1331T>G	p.Val444Gly	missense_variant	Exon 13 of 28	ENST00000650372.1	NP_003733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000650372.1	c.1331T>G	p.Val444Gly	missense_variant	Exon 13 of 28		NM_003742.4	ENSP00000497931.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 79180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Uncertain	0.47	T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.0078
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.78	.;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Uncertain	-0.00080	T
MutationAssessor	Benign	0.81	L;L
PhyloP100		2.4
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	N;.
REVEL	Uncertain	0.41
Sift	Benign	0.11	T;.
Sift4G	Benign	0.25	T;.
Polyphen		0.26	B;B
Vest4		0.42
MutPred		0.13		Loss of stability (P = 0.0013);Loss of stability (P = 0.0013);
MVP		0.88
MPC		0.27
ClinPred		0.33	T
GERP RS		4.6
Varity_R		0.36
gMVP		0.83
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs2287622; hg19: chr2-169830328;