rs35953143

Variant names:

• chr18-57648545-C-T
• rs35953143
• NM_001374385.1:c.3699G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-57648545-C-T
• chr18-57648545-C-A
• chr18-57648545-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001374385.1(ATP8B1):​c.3699G>A​(p.Pro1233Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,611,554 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00079 (16 hom.)
• Consequence: ATP8B1 NM_001374385.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -7.28
• Publications: 2 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=-0.65).
• BP6: Variant 18-57648545-C-T is Benign according to our data. Variant chr18-57648545-C-T is described in ClinVar as Benign. ClinVar VariationId is 259824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-7.28 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00728 (1110/152374) while in subpopulation AFR AF = 0.025 (1040/41592). AF 95% confidence interval is 0.0237. There are 11 homozygotes in GnomAd4. There are 515 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 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.3699G>A	p.Pro1233Pro	synonymous	Exon 28 of 28	NP_001361314.1	O43520
	ATP8B1	NM_005603.6		c.3699G>A	p.Pro1233Pro	synonymous	Exon 28 of 28	NP_005594.2	O43520
	ATP8B1	NM_001374386.1		c.3549G>A	p.Pro1183Pro	synonymous	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.3699G>A	p.Pro1233Pro	synonymous	Exon 28 of 28	ENSP00000497896.1	O43520
	ATP8B1-AS1	ENST00000592201.2	TSL:1	n.722+6493C>T		intron	N/A
	ATP8B1	ENST00000857621.1		c.3699G>A	p.Pro1233Pro	synonymous	Exon 28 of 28	ENSP00000527680.1

Frequencies

GnomAD3 genomes AF: 0.00730 AC: 1111 AN: 152256 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00204 AC: 503 AN: 246050 AF XY: 0.00163

Gnomad AFR exome AF: 0.0251

Gnomad AMR exome AF: 0.00238

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000137

Gnomad OTH exome AF: 0.00216

GnomAD4 exome AF: 0.000794 AC: 1159 AN: 1459180 Hom.: 16 Cov.: 31 AF XY: 0.000682 AC XY: 495 AN XY: 725928

African (AFR) AF: 0.0256 AC: 856 AN: 33410

American (AMR) AF: 0.00255 AC: 114 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52778

Middle Eastern (MID) AF: 0.00241 AC: 10 AN: 4142

European-Non Finnish (NFE) AF: 0.0000585 AC: 65 AN: 1111940

Other (OTH) AF: 0.00174 AC: 105 AN: 60212

GnomAD4 genome AF: 0.00728 AC: 1110 AN: 152374 Hom.: 11 Cov.: 32 AF XY: 0.00691 AC XY: 515 AN XY: 74512

African (AFR) AF: 0.0250 AC: 1040 AN: 41592

American (AMR) AF: 0.00314 AC: 48 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68040

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00378 Hom.: 2

Bravo AF: 0.00835

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000296

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	-0.65
CADD	Benign	0.81
DANN	Benign	0.82
PhyloP100		-7.3
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: rs35953143; hg19: chr18-55315777;