NM_024837.4:c.3027+4621T>C

Variant names:

• chr15-49871657-A-G
• rs8041979
• NM_024837.4:c.3027+4621T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024837.4(ATP8B4):​c.3027+4621T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,998 control chromosomes in the GnomAD database, including 7,998 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7998 hom., cov: 32)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387
• Publications: 2 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 (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 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.3027+4621T>C		intron	N/A	NP_079113.2
	ATP8B4	NR_073596.2		n.3079+4621T>C		intron	N/A
	ATP8B4	NR_073597.2		n.3032+4621T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	ENST00000284509.11	TSL:5 MANE Select	c.3027+4621T>C		intron	N/A	ENSP00000284509.6
	ATP8B4	ENST00000557955.5	TSL:1	n.*725+4621T>C		intron	N/A	ENSP00000453690.1
	ATP8B4	ENST00000558498.5	TSL:1	n.299+4621T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46960 AN: 151880 Hom.: 7965 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.0442

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.295

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.309 AC: 47040 AN: 151998 Hom.: 7998 Cov.: 32 AF XY: 0.302 AC XY: 22453 AN XY: 74278

African (AFR) AF: 0.439 AC: 18177 AN: 41440

American (AMR) AF: 0.232 AC: 3544 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 851 AN: 3470

East Asian (EAS) AF: 0.0440 AC: 227 AN: 5164

South Asian (SAS) AF: 0.226 AC: 1086 AN: 4804

European-Finnish (FIN) AF: 0.256 AC: 2707 AN: 10564

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19405 AN: 67960

Other (OTH) AF: 0.291 AC: 615 AN: 2112

Alfa AF: 0.264 Hom.: 2856

Bravo AF: 0.311

Asia WGS AF: 0.139 AC: 487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.85
PhyloP100		0.39
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: rs8041979; hg19: chr15-50163854;