1-154344677-C-T

Variant names:

• chr1-154344677-C-T
• rs1194587
• NM_001370597.1:c.2178C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001370597.1(ATP8B2):​c.2178C>T​(p.Ser726Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,610,510 control chromosomes in the GnomAD database, including 171,551 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 0.39 (13308 hom., cov: 31)
  • Exomes 𝑓: 0.46 (158243 hom.)
• Consequence: ATP8B2 NM_001370597.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.68
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-3.68 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370597.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B2	NM_001370597.1	MANE Select	c.2178C>T	p.Ser726Ser	synonymous	Exon 21 of 28	NP_001357526.1	P98198-5
	ATP8B2	NM_001367934.1		c.2235C>T	p.Ser745Ser	synonymous	Exon 20 of 27	NP_001354863.1	P98198-1
	ATP8B2	NM_001370596.1		c.2181C>T	p.Ser727Ser	synonymous	Exon 21 of 28	NP_001357525.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B2	ENST00000368489.6	TSL:1 MANE Select	c.2178C>T	p.Ser726Ser	synonymous	Exon 21 of 28	ENSP00000357475.4	P98198-5
	ATP8B2	ENST00000972148.1		c.2289C>T	p.Ser763Ser	synonymous	Exon 22 of 29	ENSP00000642207.1
	ATP8B2	ENST00000672630.1		c.2277C>T	p.Ser759Ser	synonymous	Exon 21 of 28	ENSP00000500034.1	P98198-3

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59648 AN: 151878 Hom.: 13309 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.447

GnomAD2 exomes AF: 0.470 AC: 118017 AN: 251300 AF XY: 0.475

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.506

Gnomad ASJ exome AF: 0.583

Gnomad EAS exome AF: 0.607

Gnomad FIN exome AF: 0.422

Gnomad NFE exome AF: 0.473

Gnomad OTH exome AF: 0.479

GnomAD4 exome AF: 0.462 AC: 673183 AN: 1458514 Hom.: 158243 Cov.: 59 AF XY: 0.464 AC XY: 336278 AN XY: 724806

African (AFR) AF: 0.157 AC: 5252 AN: 33446

American (AMR) AF: 0.507 AC: 22620 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 15208 AN: 26112

East Asian (EAS) AF: 0.601 AC: 23800 AN: 39568

South Asian (SAS) AF: 0.493 AC: 42500 AN: 86214

European-Finnish (FIN) AF: 0.428 AC: 22853 AN: 53394

Middle Eastern (MID) AF: 0.514 AC: 2962 AN: 5766

European-Non Finnish (NFE) AF: 0.460 AC: 510324 AN: 1109188

Other (OTH) AF: 0.460 AC: 27664 AN: 60186

GnomAD4 genome AF: 0.393 AC: 59665 AN: 151996 Hom.: 13308 Cov.: 31 AF XY: 0.395 AC XY: 29323 AN XY: 74278

African (AFR) AF: 0.169 AC: 7019 AN: 41454

American (AMR) AF: 0.490 AC: 7489 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2084 AN: 3466

East Asian (EAS) AF: 0.608 AC: 3140 AN: 5164

South Asian (SAS) AF: 0.518 AC: 2499 AN: 4820

European-Finnish (FIN) AF: 0.419 AC: 4426 AN: 10554

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31492 AN: 67950

Other (OTH) AF: 0.441 AC: 931 AN: 2110

Alfa AF: 0.446 Hom.: 30266

Bravo AF: 0.391

Asia WGS AF: 0.520 AC: 1808 AN: 3478

EpiCase AF: 0.474

EpiControl AF: 0.482

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.16
DANN	Benign	0.62
PhyloP100		-3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1194587; hg19: chr1-154317153; COSMIC: COSV59246046; COSMIC: COSV59246046;