18-57695300-T-G

Variant names:

• chr18-57695300-T-G
• rs319443
• NM_001374385.1:c.811A>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001374385.1(ATP8B1):​c.811A>C​(p.Arg271Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 1,607,586 control chromosomes in the GnomAD database, including 801,384 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (74883 hom., cov: 33)
  • Exomes 𝑓: 1.0 (726501 hom.)
• Consequence: ATP8B1 NM_001374385.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 2.30
• Publications: 21 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 18-57695300-T-G is Benign according to our data. Variant chr18-57695300-T-G is described in ClinVar as Benign. ClinVar VariationId is 259828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.3 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) 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.811A>C	p.Arg271Arg	synonymous	Exon 10 of 28	NP_001361314.1	O43520
	ATP8B1	NM_005603.6		c.811A>C	p.Arg271Arg	synonymous	Exon 10 of 28	NP_005594.2	O43520
	ATP8B1	NM_001374386.1		c.661A>C	p.Arg221Arg	synonymous	Exon 9 of 27	NP_001361315.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B1	ENST00000648908.2	MANE Select	c.811A>C	p.Arg271Arg	synonymous	Exon 10 of 28	ENSP00000497896.1	O43520
	ATP8B1	ENST00000857621.1		c.811A>C	p.Arg271Arg	synonymous	Exon 10 of 28	ENSP00000527680.1
	ATP8B1	ENST00000857625.1		c.811A>C	p.Arg271Arg	synonymous	Exon 11 of 29	ENSP00000527684.1

Frequencies

GnomAD3 genomes AF: 0.992 AC: 150869 AN: 152130 Hom.: 74829 Cov.: 33

Gnomad AFR AF: 0.971

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.997

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: 0.994

GnomAD2 exomes AF: 0.998 AC: 250737 AN: 251286 AF XY: 0.998

Gnomad AFR exome AF: 0.971

Gnomad AMR exome AF: 0.998

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: 1454155 AN: 1455338 Hom.: 726501 Cov.: 43 AF XY: 0.999 AC XY: 723934 AN XY: 724460

African (AFR) AF: 0.972 AC: 32370 AN: 33310

American (AMR) AF: 0.998 AC: 44629 AN: 44704

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26077 AN: 26082

East Asian (EAS) AF: 1.00 AC: 39647 AN: 39648

South Asian (SAS) AF: 1.00 AC: 86102 AN: 86108

European-Finnish (FIN) AF: 1.00 AC: 53416 AN: 53416

Middle Eastern (MID) AF: 0.999 AC: 5758 AN: 5764

European-Non Finnish (NFE) AF: 1.00 AC: 1106092 AN: 1106136

Other (OTH) AF: 0.998 AC: 60064 AN: 60170

GnomAD4 genome AF: 0.992 AC: 150982 AN: 152248 Hom.: 74883 Cov.: 33 AF XY: 0.992 AC XY: 73859 AN XY: 74436

African (AFR) AF: 0.971 AC: 40344 AN: 41532

American (AMR) AF: 0.997 AC: 15241 AN: 15294

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

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5182

South Asian (SAS) AF: 1.00 AC: 4824 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10586 AN: 10586

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

European-Non Finnish (NFE) AF: 1.00 AC: 68027 AN: 68036

Other (OTH) AF: 0.994 AC: 2101 AN: 2114

Alfa AF: 0.996 Hom.: 112037

Bravo AF: 0.991

Asia WGS AF: 0.999 AC: 3472 AN: 3476

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	-0.49
CADD	Benign	8.7
DANN	Benign	0.73
PhyloP100		2.3
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: rs319443; hg19: chr18-55362532; COSMIC: COSV108052764; COSMIC: COSV108052764;