rs34255016

Variant names:

• chr18-57648477-G-A
• rs34255016
• NM_001374385.1:c.*11C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001374385.1(ATP8B1):​c.*11C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,610,924 control chromosomes in the GnomAD database, including 216 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0097 (23 hom., cov: 32)
  • Exomes 𝑓: 0.015 (193 hom.)
• Consequence: ATP8B1 NM_001374385.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.67
• Publications: 4 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=-0.86).
• BP6: Variant 18-57648477-G-A is Benign according to our data. Variant chr18-57648477-G-A is described in ClinVar as Benign. ClinVar VariationId is 259814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0097 (1477/152346) while in subpopulation NFE AF = 0.015 (1018/68032). AF 95% confidence interval is 0.0142. There are 23 homozygotes in GnomAd4. There are 677 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 AR,Unknown gene

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.*11C>T		3_prime_UTR	Exon 28 of 28	NP_001361314.1	O43520
	ATP8B1	NM_005603.6		c.*11C>T		3_prime_UTR	Exon 28 of 28	NP_005594.2	O43520
	ATP8B1	NM_001374386.1		c.*11C>T		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.*11C>T		3_prime_UTR	Exon 28 of 28	ENSP00000497896.1	O43520
	ATP8B1-AS1	ENST00000592201.2	TSL:1	n.722+6425G>A		intron	N/A
	ATP8B1	ENST00000857621.1		c.*11C>T		3_prime_UTR	Exon 28 of 28	ENSP00000527680.1

Frequencies

GnomAD3 genomes AF: 0.00971 AC: 1478 AN: 152228 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.00258

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.00988

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00943 AC: 2291 AN: 243008 AF XY: 0.00943

Gnomad AFR exome AF: 0.00256

Gnomad AMR exome AF: 0.00726

Gnomad ASJ exome AF: 0.0192

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00259

Gnomad NFE exome AF: 0.0147

Gnomad OTH exome AF: 0.0126

GnomAD4 exome AF: 0.0146 AC: 21348 AN: 1458578 Hom.: 193 Cov.: 31 AF XY: 0.0145 AC XY: 10506 AN XY: 725604

African (AFR) AF: 0.00269 AC: 90 AN: 33406

American (AMR) AF: 0.00771 AC: 345 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 565 AN: 26130

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.00385 AC: 332 AN: 86168

European-Finnish (FIN) AF: 0.00308 AC: 161 AN: 52310

Middle Eastern (MID) AF: 0.0198 AC: 82 AN: 4140

European-Non Finnish (NFE) AF: 0.0171 AC: 18985 AN: 1111794

Other (OTH) AF: 0.0131 AC: 786 AN: 60212

GnomAD4 genome AF: 0.00970 AC: 1477 AN: 152346 Hom.: 23 Cov.: 32 AF XY: 0.00909 AC XY: 677 AN XY: 74494

African (AFR) AF: 0.00257 AC: 107 AN: 41588

American (AMR) AF: 0.00987 AC: 151 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4830

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10618

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.0150 AC: 1018 AN: 68032

Other (OTH) AF: 0.0123 AC: 26 AN: 2116

Alfa AF: 0.0142 Hom.: 16

Bravo AF: 0.0108

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	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	-0.86
CADD	Benign	0.19
DANN	Benign	0.72
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

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: rs34255016; hg19: chr18-55315709;