2-168979878-C-A

Variant names:

• chr2-168979878-C-A
• rs57509552
• NM_003742.4:c.1185G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003742.4(ABCB11):​c.1185G>T​(p.Glu395Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,427,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ABCB11 NM_003742.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09815356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB11	NM_003742.4	c.1185G>T	p.Glu395Asp	missense_variant	Exon 11 of 28	ENST00000650372.1	NP_003733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000650372.1	c.1185G>T	p.Glu395Asp	missense_variant	Exon 11 of 28		NM_003742.4	ENSP00000497931.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1427420 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 709624

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.17e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.22	T;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.60
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.66	.;T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.098	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.63	N;.
REVEL	Benign	0.12
Sift	Benign	0.31	T;.
Sift4G	Benign	0.36	T;.
Polyphen		0.0020	B;B
Vest4		0.22
MutPred		0.40		Loss of methylation at K400 (P = 0.135);Loss of methylation at K400 (P = 0.135);
MVP		0.72
MPC		0.13
ClinPred		0.13	T
GERP RS		-1.7
Varity_R		0.055
gMVP		0.82

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: rs57509552; hg19: chr2-169836388;