rs34027711

Variant names:

• chr18-57650359-C-A
• rs34027711
• NM_001374385.1:c.3531+8G>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.3531+8G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,611,714 control chromosomes in the GnomAD database, including 20,984 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1453 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19531 hom.)
• Consequence: ATP8B1 NM_001374385.1 splice_region, intron
• Scores: Splicing: ADA: 0.0001719
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.578
• 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=-0.8).
• BP6: Variant 18-57650359-C-A is Benign according to our data. Variant chr18-57650359-C-A is described in ClinVar as Benign. ClinVar VariationId is 259822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 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.3531+8G>T		splice_region intron	N/A	NP_001361314.1	O43520
	ATP8B1	NM_005603.6		c.3531+8G>T		splice_region intron	N/A	NP_005594.2	O43520
	ATP8B1	NM_001374386.1		c.3381+8G>T		splice_region 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.3531+8G>T		splice_region intron	N/A	ENSP00000497896.1	O43520
	ATP8B1-AS1	ENST00000592201.2	TSL:1	n.722+8307C>A		intron	N/A
	ATP8B1	ENST00000857621.1		c.3531+8G>T		splice_region intron	N/A	ENSP00000527680.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18489 AN: 152064 Hom.: 1453 Cov.: 32

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.00845

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.139

GnomAD2 exomes AF: 0.140 AC: 35128 AN: 251462 AF XY: 0.144

Gnomad AFR exome AF: 0.0295

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.203

Gnomad EAS exome AF: 0.00549

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.172

Gnomad OTH exome AF: 0.152

GnomAD4 exome AF: 0.159 AC: 232074 AN: 1459532 Hom.: 19531 Cov.: 31 AF XY: 0.158 AC XY: 115035 AN XY: 726112

African (AFR) AF: 0.0256 AC: 855 AN: 33416

American (AMR) AF: 0.144 AC: 6442 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 5142 AN: 26078

East Asian (EAS) AF: 0.00546 AC: 216 AN: 39578

South Asian (SAS) AF: 0.136 AC: 11702 AN: 86188

European-Finnish (FIN) AF: 0.139 AC: 7382 AN: 53150

Middle Eastern (MID) AF: 0.139 AC: 800 AN: 5752

European-Non Finnish (NFE) AF: 0.172 AC: 190854 AN: 1110490

Other (OTH) AF: 0.144 AC: 8681 AN: 60232

GnomAD4 genome AF: 0.121 AC: 18484 AN: 152182 Hom.: 1453 Cov.: 32 AF XY: 0.120 AC XY: 8891 AN XY: 74396

African (AFR) AF: 0.0313 AC: 1301 AN: 41530

American (AMR) AF: 0.154 AC: 2344 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 668 AN: 3470

East Asian (EAS) AF: 0.00847 AC: 44 AN: 5194

South Asian (SAS) AF: 0.127 AC: 610 AN: 4822

European-Finnish (FIN) AF: 0.144 AC: 1522 AN: 10582

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11615 AN: 68002

Other (OTH) AF: 0.136 AC: 287 AN: 2108

Alfa AF: 0.154 Hom.: 1232

Bravo AF: 0.117

Asia WGS AF: 0.0700 AC: 245 AN: 3478

EpiCase AF: 0.166

EpiControl AF: 0.169

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	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	-0.80
CADD	Benign	7.4
DANN	Benign	0.37
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00017
dbscSNV1_RF	Benign	0.016
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: -34

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34027711; hg19: chr18-55317591;