NM_001374385.1:c.*1723G>A

Variant names:

• chr18-57646765-C-T
• rs11543269
• NM_001374385.1:c.*1723G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001374385.1(ATP8B1):​c.*1723G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 152,636 control chromosomes in the GnomAD database, including 701 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.089 (698 hom., cov: 33)
  • Exomes 𝑓: 0.11 (3 hom.)
• Consequence: ATP8B1 NM_001374385.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.65
• Publications: 6 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 18-57646765-C-T is Benign according to our data. Variant chr18-57646765-C-T is described in ClinVar as Benign. ClinVar VariationId is 327441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 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.*1723G>A		3_prime_UTR	Exon 28 of 28	NP_001361314.1	O43520
	ATP8B1	NM_005603.6		c.*1723G>A		3_prime_UTR	Exon 28 of 28	NP_005594.2	O43520
	ATP8B1	NM_001374386.1		c.*1723G>A		3_prime_UTR	Exon 27 of 27	NP_001361315.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B1	ENST00000648908.2	MANE Select	c.*1723G>A		3_prime_UTR	Exon 28 of 28	ENSP00000497896.1	O43520
	ATP8B1-AS1	ENST00000592201.2	TSL:1	n.722+4713C>T		intron	N/A
	ATP8B1	ENST00000857621.1		c.*1723G>A		3_prime_UTR	Exon 28 of 28	ENSP00000527680.1

Frequencies

GnomAD3 genomes AF: 0.0888 AC: 13500 AN: 152088 Hom.: 697 Cov.: 33

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.0688

Gnomad ASJ AF: 0.0861

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0563

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0846

GnomAD4 exome AF: 0.114 AC: 49 AN: 430 Hom.: 3 Cov.: 0 AF XY: 0.140 AC XY: 36 AN XY: 258

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.113 AC: 48 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0887 AC: 13499 AN: 152206 Hom.: 698 Cov.: 33 AF XY: 0.0872 AC XY: 6486 AN XY: 74416

African (AFR) AF: 0.0601 AC: 2497 AN: 41538

American (AMR) AF: 0.0687 AC: 1051 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0861 AC: 299 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0561 AC: 271 AN: 4830

European-Finnish (FIN) AF: 0.107 AC: 1132 AN: 10572

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7791 AN: 67992

Other (OTH) AF: 0.0837 AC: 177 AN: 2114

Alfa AF: 0.101 Hom.: 312

Bravo AF: 0.0857

Asia WGS AF: 0.0330 AC: 115 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Progressive familial intrahepatic cholestasis type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Benign	0.66
PhyloP100		1.6
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: rs11543269; hg19: chr18-55313997;