rs2271771

Variant names:

• chr18-57648500-G-T
• rs2271771
• NM_001374385.1:c.3744C>A

Your query was ambiguous. Multiple possible variants found:

• chr18-57648500-G-T
• chr18-57648500-G-A
• chr18-57648500-G-C

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.3744C>A​(p.Thr1248Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,611,248 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (10 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (64 hom.)
• Consequence: ATP8B1 NM_001374385.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -3.82
• Publications: 5 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=-0.82).
• BP6: Variant 18-57648500-G-T is Benign according to our data. Variant chr18-57648500-G-T is described in ClinVar as Benign. ClinVar VariationId is 259825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.82 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00194 (295/152336) while in subpopulation EAS AF = 0.0452 (234/5182). AF 95% confidence interval is 0.0404. There are 10 homozygotes in GnomAd4. There are 174 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 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.3744C>A	p.Thr1248Thr	synonymous	Exon 28 of 28	NP_001361314.1	O43520
	ATP8B1	NM_005603.6		c.3744C>A	p.Thr1248Thr	synonymous	Exon 28 of 28	NP_005594.2	O43520
	ATP8B1	NM_001374386.1		c.3594C>A	p.Thr1198Thr	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.3744C>A	p.Thr1248Thr	synonymous	Exon 28 of 28	ENSP00000497896.1	O43520
	ATP8B1-AS1	ENST00000592201.2	TSL:1	n.722+6448G>T		intron	N/A
	ATP8B1	ENST00000857621.1		c.3744C>A	p.Thr1248Thr	synonymous	Exon 28 of 28	ENSP00000527680.1

Frequencies

GnomAD3 genomes AF: 0.00194 AC: 296 AN: 152218 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0452

Gnomad SAS AF: 0.00372

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00409 AC: 999 AN: 244102 AF XY: 0.00380

Gnomad AFR exome AF: 0.000518

Gnomad AMR exome AF: 0.000377

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0486

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000834

Gnomad OTH exome AF: 0.00134

GnomAD4 exome AF: 0.00171 AC: 2495 AN: 1458912 Hom.: 64 Cov.: 31 AF XY: 0.00175 AC XY: 1267 AN XY: 725758

African (AFR) AF: 0.000299 AC: 10 AN: 33410

American (AMR) AF: 0.000358 AC: 16 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0509 AC: 2019 AN: 39694

South Asian (SAS) AF: 0.00250 AC: 215 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52484

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

European-Non Finnish (NFE) AF: 0.0000917 AC: 102 AN: 1111954

Other (OTH) AF: 0.00204 AC: 123 AN: 60208

GnomAD4 genome AF: 0.00194 AC: 295 AN: 152336 Hom.: 10 Cov.: 33 AF XY: 0.00234 AC XY: 174 AN XY: 74486

African (AFR) AF: 0.000409 AC: 17 AN: 41570

American (AMR) AF: 0.000915 AC: 14 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0452 AC: 234 AN: 5182

South Asian (SAS) AF: 0.00393 AC: 19 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68036

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000389 Hom.: 1

Bravo AF: 0.00194

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Progressive familial intrahepatic cholestasis type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.010
DANN	Benign	0.64
PhyloP100		-3.8
Mutation Taster		=99/1	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: rs2271771; hg19: chr18-55315732; COSMIC: COSV52179922;