rs319438

Variant names:

• chr18-57697620-A-G
• rs319438
• NM_001374385.1:c.696T>C

Your query was ambiguous. Multiple possible variants found:

• chr18-57697620-A-G
• chr18-57697620-A-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001374385.1(ATP8B1):​c.696T>C​(p.Asp232Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,613,916 control chromosomes in the GnomAD database, including 805,295 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (75238 hom., cov: 29)
  • Exomes 𝑓: 1.0 (730057 hom.)
• Consequence: ATP8B1 NM_001374385.1 splice_region, synonymous
• Scores: Splicing: ADA: 0.00002227
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.0390
• Publications: 25 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 18-57697620-A-G is Benign according to our data. Variant chr18-57697620-A-G is described in ClinVar as Benign. ClinVar VariationId is 259826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.039 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 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.696T>C	p.Asp232Asp	splice_region synonymous	Exon 8 of 28	NP_001361314.1	O43520
	ATP8B1	NM_005603.6		c.696T>C	p.Asp232Asp	splice_region synonymous	Exon 8 of 28	NP_005594.2	O43520
	ATP8B1	NM_001374386.1		c.546T>C	p.Asp182Asp	splice_region synonymous	Exon 7 of 27	NP_001361315.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B1	ENST00000648908.2	MANE Select	c.696T>C	p.Asp232Asp	splice_region synonymous	Exon 8 of 28	ENSP00000497896.1	O43520
	ATP8B1	ENST00000857621.1		c.696T>C	p.Asp232Asp	splice_region synonymous	Exon 8 of 28	ENSP00000527680.1
	ATP8B1	ENST00000857625.1		c.696T>C	p.Asp232Asp	splice_region synonymous	Exon 9 of 29	ENSP00000527684.1

Frequencies

GnomAD3 genomes AF: 0.994 AC: 151182 AN: 152032 Hom.: 75182 Cov.: 29

Gnomad AFR AF: 0.981

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.998

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.996

GnomAD2 exomes AF: 0.998 AC: 250904 AN: 251298 AF XY: 0.999

Gnomad AFR exome AF: 0.980

Gnomad AMR exome AF: 0.999

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.999

GnomAD4 exome AF: 0.999 AC: 1460930 AN: 1461766 Hom.: 730057 Cov.: 47 AF XY: 0.999 AC XY: 726823 AN XY: 727192

African (AFR) AF: 0.981 AC: 32836 AN: 33478

American (AMR) AF: 0.999 AC: 44677 AN: 44722

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26131 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39689 AN: 39700

South Asian (SAS) AF: 1.00 AC: 86252 AN: 86256

European-Finnish (FIN) AF: 1.00 AC: 53395 AN: 53400

Middle Eastern (MID) AF: 1.00 AC: 5767 AN: 5768

European-Non Finnish (NFE) AF: 1.00 AC: 1111862 AN: 1111912

Other (OTH) AF: 0.999 AC: 60321 AN: 60394

GnomAD4 genome AF: 0.994 AC: 151297 AN: 152150 Hom.: 75238 Cov.: 29 AF XY: 0.995 AC XY: 73997 AN XY: 74378

African (AFR) AF: 0.981 AC: 40691 AN: 41490

American (AMR) AF: 0.998 AC: 15252 AN: 15288

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3471 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5156 AN: 5158

South Asian (SAS) AF: 1.00 AC: 4791 AN: 4792

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10618

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68006 AN: 68012

Other (OTH) AF: 0.996 AC: 2106 AN: 2114

Alfa AF: 0.998 Hom.: 103586

Bravo AF: 0.994

Asia WGS AF: 0.999 AC: 3475 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	not provided (2)
-	-	2	Progressive familial intrahepatic cholestasis type 1 (2)
-	-	1	Cholestasis, intrahepatic, of pregnancy, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	0.78
DANN	Benign	0.80
PhyloP100		-0.039
Mutation Taster		=81/19	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
dbscSNV1_RF	Benign	0.0020
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: rs319438; hg19: chr18-55364852;