rs6702754

Positions:

• chr1-154331500-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001370597.1(ATP8B2):​c.360T>C​(p.Asn120=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,613,738 control chromosomes in the GnomAD database, including 76,216 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 0.30 (6941 hom., cov: 32)
  • Exomes 𝑓: 0.31 (69275 hom.)
• Consequence: ATP8B2 NM_001370597.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334

Genes affected

ATP8B2 (HGNC:13534): (ATPase phospholipid transporting 8B2) The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of aminophospholipid-transporting ATPases. The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=0.334 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8B2	NM_001370597.1	c.360T>C	p.Asn120=	synonymous_variant	6/28	ENST00000368489.6	NP_001357526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP8B2	ENST00000368489.6	c.360T>C	p.Asn120=	synonymous_variant	6/28	1	NM_001370597.1	ENSP00000357475	P1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45737 AN: 151958 Hom.: 6931 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.287

GnomAD3 exomes AF: 0.292 AC: 73402 AN: 251466 Hom.: 11145 AF XY: 0.299 AC XY: 40606 AN XY: 135912

Gnomad AFR exome AF: 0.314

Gnomad AMR exome AF: 0.214

Gnomad ASJ exome AF: 0.208

Gnomad EAS exome AF: 0.226

Gnomad SAS exome AF: 0.343

Gnomad FIN exome AF: 0.367

Gnomad NFE exome AF: 0.303

Gnomad OTH exome AF: 0.287

GnomAD4 exome AF: 0.305 AC: 446234 AN: 1461662 Hom.: 69275 Cov.: 39 AF XY: 0.307 AC XY: 223351 AN XY: 727136

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.227

Gnomad4 SAS exome AF: 0.345

Gnomad4 FIN exome AF: 0.361

Gnomad4 NFE exome AF: 0.308

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.301 AC: 45780 AN: 152076 Hom.: 6941 Cov.: 32 AF XY: 0.304 AC XY: 22569 AN XY: 74352

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.292

Alfa AF: 0.299 Hom.: 16430

Bravo AF: 0.289

Asia WGS AF: 0.271 AC: 940 AN: 3478

EpiCase AF: 0.299

EpiControl AF: 0.299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	10
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs6702754; hg19: chr1-154303976; COSMIC: COSV59245669; COSMIC: COSV59245669;