NM_001374385.1:c.698+20C>T

Variant names:

• chr18-57697598-G-A
• rs319439
• NM_001374385.1:c.698+20C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001374385.1(ATP8B1):​c.698+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,608,944 control chromosomes in the GnomAD database, including 184,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15074 hom., cov: 31)
  • Exomes 𝑓: 0.48 (169620 hom.)
• Consequence: ATP8B1 NM_001374385.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.221
• Publications: 10 publications found

Genes affected

ATP8B1 (HGNC:3706): (ATPase phospholipid transporting 8B1) This gene encodes a member of the P-type cation transport ATPase family, which belongs to the subfamily of aminophospholipid-transporting ATPases. The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. Mutations in this gene may result in progressive familial intrahepatic cholestasis type 1 and in benign recurrent intrahepatic cholestasis. [provided by RefSeq, Jul 2008]

ATP8B1-AS1 (HGNC:56042): (ATP8B1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 18-57697598-G-A is Benign according to our data. Variant chr18-57697598-G-A is described in ClinVar as Benign. ClinVar VariationId is 259827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374385.1. 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
	ATP8B1	NM_001374385.1	MANE Select	c.698+20C>T		intron	N/A	NP_001361314.1	O43520
	ATP8B1	NM_005603.6		c.698+20C>T		intron	N/A	NP_005594.2	O43520
	ATP8B1	NM_001374386.1		c.548+20C>T		intron	N/A	NP_001361315.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B1	ENST00000648908.2	MANE Select	c.698+20C>T		intron	N/A	ENSP00000497896.1	O43520
	ATP8B1	ENST00000857621.1		c.698+20C>T		intron	N/A	ENSP00000527680.1
	ATP8B1	ENST00000857625.1		c.698+20C>T		intron	N/A	ENSP00000527684.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65310 AN: 151782 Hom.: 15055 Cov.: 31

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.451

GnomAD2 exomes AF: 0.487 AC: 122250 AN: 250774 AF XY: 0.480

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.647

Gnomad ASJ exome AF: 0.536

Gnomad EAS exome AF: 0.677

Gnomad FIN exome AF: 0.445

Gnomad NFE exome AF: 0.472

Gnomad OTH exome AF: 0.498

GnomAD4 exome AF: 0.477 AC: 694706 AN: 1457044 Hom.: 169620 Cov.: 33 AF XY: 0.474 AC XY: 343967 AN XY: 725166

African (AFR) AF: 0.253 AC: 8438 AN: 33386

American (AMR) AF: 0.638 AC: 28508 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 13817 AN: 26102

East Asian (EAS) AF: 0.711 AC: 28217 AN: 39666

South Asian (SAS) AF: 0.380 AC: 32782 AN: 86168

European-Finnish (FIN) AF: 0.446 AC: 23764 AN: 53318

Middle Eastern (MID) AF: 0.406 AC: 2336 AN: 5748

European-Non Finnish (NFE) AF: 0.477 AC: 528068 AN: 1107688

Other (OTH) AF: 0.478 AC: 28776 AN: 60254

GnomAD4 genome AF: 0.430 AC: 65360 AN: 151900 Hom.: 15074 Cov.: 31 AF XY: 0.430 AC XY: 31892 AN XY: 74236

African (AFR) AF: 0.269 AC: 11117 AN: 41390

American (AMR) AF: 0.552 AC: 8423 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1804 AN: 3468

East Asian (EAS) AF: 0.684 AC: 3520 AN: 5148

South Asian (SAS) AF: 0.380 AC: 1822 AN: 4796

European-Finnish (FIN) AF: 0.449 AC: 4742 AN: 10564

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32574 AN: 67972

Other (OTH) AF: 0.456 AC: 963 AN: 2110

Alfa AF: 0.468 Hom.: 67230

Bravo AF: 0.438

Asia WGS AF: 0.498 AC: 1729 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Cholestasis, intrahepatic, of pregnancy, 1 (1)
-	-	1	Progressive familial intrahepatic cholestasis type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.47
PhyloP100		0.22
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: rs319439; hg19: chr18-55364830; COSMIC: COSV52175920; COSMIC: COSV52175920;