18-57706561-C-G

Variant names:

• chr18-57706561-C-G
• rs34719006
• NM_001374385.1:c.208G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001374385.1(ATP8B1):​c.208G>C​(p.Asp70His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. D70N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP8B1 NM_001374385.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.18
• Publications: 0 publications found

Genes affected

ATP8B1 (HGNC:3706): (ATPase phospholipid transporting 8B1) This gene encodes a member of the P-type cation transport ATPase family, which belongs to the subfamily of aminophospholipid-transporting ATPases. The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. Mutations in this gene may result in progressive familial intrahepatic cholestasis type 1 and in benign recurrent intrahepatic cholestasis. [provided by RefSeq, Jul 2008]

ATP8B1-AS1 (HGNC:56042): (ATP8B1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8B1	NM_001374385.1	c.208G>C	p.Asp70His	missense_variant	Exon 3 of 28	ENST00000648908.2	NP_001361314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8B1	ENST00000648908.2	c.208G>C	p.Asp70His	missense_variant	Exon 3 of 28		NM_001374385.1	ENSP00000497896.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.4	M;M
PhyloP100		5.2
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-4.7	D;.
REVEL	Uncertain	0.31
Sift	Uncertain	0.0020	D;.
Sift4G	Uncertain	0.0080	D;.
Polyphen		1.0	D;D
Vest4		0.65
MutPred		0.35		Gain of MoRF binding (P = 0.0415);Gain of MoRF binding (P = 0.0415);
MVP		0.82
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.57
gMVP		0.68

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: rs34719006; hg19: chr18-55373793;