15-49934116-G-T

Variant names:

• chr15-49934116-G-T
• rs2452524
• NM_024837.4:c.1354C>A

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 34 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024837.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	NM_024837.4	MANE Select	c.1354C>A	p.His452Asn	missense	Exon 15 of 28	NP_079113.2
	ATP8B4	NR_073596.2		n.1595C>A		non_coding_transcript_exon	Exon 16 of 28
	ATP8B4	NR_073597.2		n.1507C>A		non_coding_transcript_exon	Exon 15 of 27

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	ENST00000284509.11	TSL:5 MANE Select	c.1354C>A	p.His452Asn	missense	Exon 15 of 28	ENSP00000284509.6
	ATP8B4	ENST00000557955.5	TSL:1	n.1354C>A		non_coding_transcript_exon	Exon 15 of 27	ENSP00000453690.1
	ATP8B4	ENST00000558906.5	TSL:1	n.*1073C>A		non_coding_transcript_exon	Exon 16 of 28	ENSP00000452956.1

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

GnomAD2 exomes AF: 0.655 AC: 163716 AN: 249878 AF XY: 0.654

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 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

African (AFR) AF: 0.847 AC: 28283 AN: 33376

American (AMR) AF: 0.538 AC: 23920 AN: 44486

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 16902 AN: 26070

East Asian (EAS) AF: 0.432 AC: 17130 AN: 39628

South Asian (SAS) AF: 0.553 AC: 47590 AN: 86064

European-Finnish (FIN) AF: 0.789 AC: 42059 AN: 53340

Middle Eastern (MID) AF: 0.720 AC: 4140 AN: 5752

European-Non Finnish (NFE) AF: 0.702 AC: 780454 AN: 1110970

Other (OTH) AF: 0.677 AC: 40828 AN: 60308

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

African (AFR) AF: 0.836 AC: 34698 AN: 41504

American (AMR) AF: 0.604 AC: 9198 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2240 AN: 3468

East Asian (EAS) AF: 0.417 AC: 2137 AN: 5124

South Asian (SAS) AF: 0.555 AC: 2673 AN: 4814

European-Finnish (FIN) AF: 0.798 AC: 8442 AN: 10574

Middle Eastern (MID) AF: 0.695 AC: 203 AN: 292

European-Non Finnish (NFE) AF: 0.697 AC: 47337 AN: 67886

Other (OTH) AF: 0.675 AC: 1426 AN: 2114

Alfa AF: 0.694 Hom.: 84950

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 v4.9

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
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
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.53
PrimateAI	Benign	0.23	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.066
Sift	Benign	0.44	T
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.035
MPC		0.055
ClinPred		0.0088	T
GERP RS		-2.7
Varity_R		0.044
gMVP		0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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