chr15-49934116-G-T

Position:

• chr15-49934116-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024837.4(ATP8B4):​c.1354C>A​(p.His452Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 1,611,906 control chromosomes in the GnomAD database, including 387,023 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.72 (39825 hom., cov: 33)
  • Exomes 𝑓: 0.69 (347198 hom.)
• Consequence: ATP8B4 NM_024837.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.533

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.217864E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8B4	NM_024837.4	c.1354C>A	p.His452Asn	missense_variant	15/28	ENST00000284509.11	NP_079113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP8B4	ENST00000284509.11	c.1354C>A	p.His452Asn	missense_variant	15/28	5	NM_024837.4	ENSP00000284509.6

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108843 AN: 151794 Hom.: 39790 Cov.: 33

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.676

GnomAD3 exomes AF: 0.655 AC: 163716 AN: 249878 Hom.: 55249 AF XY: 0.654 AC XY: 88348 AN XY: 135138

Gnomad AFR exome AF: 0.842

Gnomad AMR exome AF: 0.529

Gnomad ASJ exome AF: 0.653

Gnomad EAS exome AF: 0.425

Gnomad SAS exome AF: 0.548

Gnomad FIN exome AF: 0.799

Gnomad NFE exome AF: 0.705

Gnomad OTH exome AF: 0.671

GnomAD4 exome AF: 0.686 AC: 1001306 AN: 1459994 Hom.: 347198 Cov.: 51 AF XY: 0.682 AC XY: 495683 AN XY: 726334

Gnomad4 AFR exome AF: 0.847

Gnomad4 AMR exome AF: 0.538

Gnomad4 ASJ exome AF: 0.648

Gnomad4 EAS exome AF: 0.432

Gnomad4 SAS exome AF: 0.553

Gnomad4 FIN exome AF: 0.789

Gnomad4 NFE exome AF: 0.702

Gnomad4 OTH exome AF: 0.677

GnomAD4 genome AF: 0.717 AC: 108933 AN: 151912 Hom.: 39825 Cov.: 33 AF XY: 0.713 AC XY: 52933 AN XY: 74232

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.675

Alfa AF: 0.689 Hom.: 60811

Bravo AF: 0.709

TwinsUK AF: 0.694 AC: 2574

ALSPAC AF: 0.690 AC: 2658

ESP6500AA AF: 0.829 AC: 3640

ESP6500EA AF: 0.700 AC: 6015

ExAC AF: 0.661 AC: 80314

Asia WGS AF: 0.520 AC: 1811 AN: 3476

EpiCase AF: 0.691

EpiControl AF: 0.698

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.3
DANN	Benign	0.41
DEOGEN2	Benign	0.00063	T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.010	T;.
MetaRNN	Benign	0.0000012	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	1.6	N;N
REVEL	Benign	0.066
Sift	Benign	0.44	T;T
Sift4G	Benign	0.49	T;T
Polyphen		0.0	B;B
Vest4		0.035
MPC		0.055
ClinPred		0.0088	T
GERP RS		-2.7
Varity_R		0.044
gMVP		0.20

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

Other links and lift over

dbSNP: rs2452524; hg19: chr15-50226313; COSMIC: COSV52715703; COSMIC: COSV52715703;