Genetic Variant ATP8B1:c.*2015delA (chr18-57646472-AT-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001374385.1(ATP8B1):c.*2015delA variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.168 in 152,484 control chromosomes in the GnomAD database, including 2,325 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 2320 hom., cov: 29)

Exomes 𝑓: 0.16 ( 5 hom. )

Consequence

ATP8B1
NM_001374385.1 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.89

Publications

1 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 -10 ACMG points.

BP6

Variant 18-57646472-AT-A is Benign according to our data. Variant chr18-57646472-AT-A is described in ClinVar as Benign. ClinVar VariationId is 327438.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 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.*2015delA	3_prime_UTR	Exon 28 of 28	NP_001361314.1	O43520
ATP8B1	NM_005603.6		c.*2015delA	3_prime_UTR	Exon 28 of 28	NP_005594.2	O43520
ATP8B1	NM_001374386.1		c.*2015delA	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.*2015delA	3_prime_UTR	Exon 28 of 28	ENSP00000497896.1	O43520
ATP8B1-AS1	ENST00000592201.2	TSL:1	n.722+4427delT	intron	N/A
ATP8B1	ENST00000857621.1		c.*2015delA	3_prime_UTR	Exon 28 of 28	ENSP00000527680.1

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25499

AN:

152012

Hom.:

2314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.110

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.153

GnomAD4 exome

AF:

0.161

AC:

AN:

354

Hom.:

Cov.:

AF XY:

0.189

AC XY:

AN XY:

212

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:

0.163

AC:

AN:

350

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.168

AC:

25520

AN:

152130

Hom.:

2320

Cov.:

AF XY:

0.168

AC XY:

12487

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.236

AC:

9772

AN:

41480

American (AMR)

AF:

0.122

AC:

1869

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

381

AN:

3472

East Asian (EAS)

AF:

0.173

AC:

900

AN:

5188

South Asian (SAS)

AF:

0.129

AC:

625

AN:

4830

European-Finnish (FIN)

AF:

0.168

AC:

1777

AN:

10572

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.140

AC:

9496

AN:

67984

Other (OTH)

AF:

0.152

AC:

322

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1071

2143

3214

4286

5357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

268

536

804

1072

1340

<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:

0.0755

Hom.:

Bravo

AF:

0.169

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Progressive familial intrahepatic cholestasis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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