Genetic Variant ATP8B1:c.*900G>T (chr18-57647588-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001374385.1(ATP8B1):c.*900G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 152,300 control chromosomes in the GnomAD database, including 16,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16451 hom., cov: 32)

Exomes 𝑓: 0.57 ( 68 hom. )

Consequence

ATP8B1
NM_001374385.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0270

Publications

3 publications found

Variant links:

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 links:

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

ATP8B1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 18-57647588-C-A is Benign according to our data. Variant chr18-57647588-C-A is described in ClinVar as Benign. ClinVar VariationId is 327449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374385.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATP8B1	NM_001374385.1	MANE Select	c.*900G>T	3_prime_UTR	Exon 28 of 28	NP_001361314.1	O43520
ATP8B1	NM_005603.6		c.*900G>T	3_prime_UTR	Exon 28 of 28	NP_005594.2	O43520
ATP8B1	NM_001374386.1		c.*900G>T	3_prime_UTR	Exon 27 of 27	NP_001361315.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATP8B1	ENST00000648908.2	MANE Select	c.*900G>T	3_prime_UTR	Exon 28 of 28	ENSP00000497896.1	O43520
ATP8B1-AS1	ENST00000592201.2	TSL:1	n.722+5536C>A	intron	N/A
ATP8B1	ENST00000857621.1		c.*900G>T	3_prime_UTR	Exon 28 of 28	ENSP00000527680.1

Frequencies

GnomAD3 genomes

AF:

0.460

AC:

69859

AN:

151764

Hom.:

16439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.379

Gnomad AMI

AF:

0.522

Gnomad AMR

AF:

0.509

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.519

Gnomad SAS

AF:

0.440

Gnomad FIN

AF:

0.562

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.479

Gnomad OTH

AF:

0.479

GnomAD4 exome

AF:

0.574

AC:

240

AN:

418

Hom.:

Cov.:

AF XY:

0.601

AC XY:

149

AN XY:

248

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.575

AC:

238

AN:

414

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.460

AC:

69912

AN:

151882

Hom.:

16451

Cov.:

AF XY:

0.464

AC XY:

34453

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.379

AC:

15694

AN:

41406

American (AMR)

AF:

0.509

AC:

7769

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.461

AC:

1600

AN:

3468

East Asian (EAS)

AF:

0.519

AC:

2679

AN:

5164

South Asian (SAS)

AF:

0.440

AC:

2117

AN:

4812

European-Finnish (FIN)

AF:

0.562

AC:

5913

AN:

10526

Middle Eastern (MID)

AF:

0.497

AC:

146

AN:

294

European-Non Finnish (NFE)

AF:

0.479

AC:

32507

AN:

67930

Other (OTH)

AF:

0.480

AC:

1011

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1937

3874

5810

7747

9684

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.406

Hom.:

2279

Bravo

AF:

0.456

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Progressive familial intrahepatic cholestasis type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.3

(source)

DANN

Benign

0.34

PhyloP100

0.027

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over