Variant chr15-49860278-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024837.4(ATP8B4):c.3495T>A(p.Asn1165Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,614,164 control chromosomes in the GnomAD database, including 356 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.027 ( 193 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 163 hom. )

Consequence

ATP8B4
NM_024837.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.70

Variant links:

Genes affected

ATP8B4 (HGNC:13536): (ATPase phospholipid transporting 8B4 (putative)) This gene encodes a member of the cation transport ATPase (P-type) family and type IV subfamily. The encoded protein is involved in phospholipid transport in the cell membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

ATP8B4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016469061).

BP6

Variant 15-49860278-A-T is Benign according to our data. Variant chr15-49860278-A-T is described in ClinVar as [Benign]. Clinvar id is 782590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8B4	NM_024837.4 linkuse as main transcript	c.3495T>A	p.Asn1165Lys	missense_variant	28/28	ENST00000284509.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8B4	ENST00000284509.11 linkuse as main transcript	c.3495T>A	p.Asn1165Lys	missense_variant	28/28	5	NM_024837.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0267

AC:

4061

AN:

152216

Hom.:

191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00609

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.00679

AC:

1706

AN:

251188

Hom.:

AF XY:

0.00497

AC XY:

674

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.0943

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00275

AC:

4017

AN:

1461830

Hom.:

163

Cov.:

AF XY:

0.00233

AC XY:

1693

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0970

Gnomad4 AMR exome

AF:

0.00409

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000533

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.0000989

Gnomad4 OTH exome

AF:

0.00661

GnomAD4 genome

AF:

0.0268

AC:

4082

AN:

152334

Hom.:

193

Cov.:

AF XY:

0.0257

AC XY:

1912

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0943

Gnomad4 AMR

AF:

0.00608

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.00390

Hom.:

Bravo

AF:

0.0307

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0888

AC:

390

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00851

AC:

1033

Asia WGS

AF:

0.0100

AC:

AN:

3476

EpiCase

AF:

0.000382

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0015

T;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.65

T;.

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

0.75

P;P

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.84

N;N

REVEL

Benign

0.047

Sift

Benign

0.46

T;T

Sift4G

Benign

0.42

T;T

Polyphen

0.049

B;B

Vest4

0.21

MutPred

0.20

Gain of solvent accessibility (P = 0.0012);Gain of solvent accessibility (P = 0.0012);

MVP

0.54

MPC

0.28

ClinPred

0.020

GERP RS

4.3

Varity_R

0.085

gMVP

0.37

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over