Genetic Variant NM_001374385.1:c.*1723G>A (chr18-57646765-C-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001374385.1(ATP8B1):c.*1723G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 152,636 control chromosomes in the GnomAD database, including 701 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 698 hom., cov: 33)

Exomes 𝑓: 0.11 ( 3 hom. )

Consequence

ATP8B1
NM_001374385.1 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.65

Publications

6 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 18-57646765-C-T is Benign according to our data. Variant chr18-57646765-C-T is described in ClinVar as Benign. ClinVar VariationId is 327441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 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.*1723G>A	3_prime_UTR	Exon 28 of 28	NP_001361314.1	O43520
ATP8B1	NM_005603.6		c.*1723G>A	3_prime_UTR	Exon 28 of 28	NP_005594.2	O43520
ATP8B1	NM_001374386.1		c.*1723G>A	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.*1723G>A	3_prime_UTR	Exon 28 of 28	ENSP00000497896.1	O43520
ATP8B1-AS1	ENST00000592201.2	TSL:1	n.722+4713C>T	intron	N/A
ATP8B1	ENST00000857621.1		c.*1723G>A	3_prime_UTR	Exon 28 of 28	ENSP00000527680.1

Frequencies

GnomAD3 genomes

AF:

0.0888

AC:

13500

AN:

152088

Hom.:

697

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0602

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.0688

Gnomad ASJ

AF:

0.0861

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0563

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.0846

GnomAD4 exome

AF:

0.114

AC:

AN:

430

Hom.:

Cov.:

AF XY:

0.140

AC XY:

AN XY:

258

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:

0.113

AC:

AN:

424

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0887

AC:

13499

AN:

152206

Hom.:

698

Cov.:

AF XY:

0.0872

AC XY:

6486

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0601

AC:

2497

AN:

41538

American (AMR)

AF:

0.0687

AC:

1051

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0861

AC:

299

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.0561

AC:

271

AN:

4830

European-Finnish (FIN)

AF:

0.107

AC:

1132

AN:

10572

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.115

AC:

7791

AN:

67992

Other (OTH)

AF:

0.0837

AC:

177

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

623

1246

1870

2493

3116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

150

300

450

600

750

<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:

0.101

Hom.:

312

Bravo

AF:

0.0857

Asia WGS

AF:

0.0330

AC:

115

AN:

3476

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

-0.43

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

1.6

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