rs12958967

Variant names:

• chr18-57648727-G-A
• rs12958967
• NM_001374385.1:c.3532-15C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-57648727-G-A
• chr18-57648727-G-C

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.3532-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,548,334 control chromosomes in the GnomAD database, including 50,815 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3745 hom., cov: 32)
  • Exomes 𝑓: 0.25 (47070 hom.)
• Consequence: ATP8B1 NM_001374385.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.271
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 18-57648727-G-A is Benign according to our data. Variant chr18-57648727-G-A is described in ClinVar as Benign. ClinVar VariationId is 259823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 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.3532-15C>T		intron	N/A	NP_001361314.1	O43520
	ATP8B1	NM_005603.6		c.3532-15C>T		intron	N/A	NP_005594.2	O43520
	ATP8B1	NM_001374386.1		c.3382-15C>T		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.3532-15C>T		intron	N/A	ENSP00000497896.1	O43520
	ATP8B1-AS1	ENST00000592201.2	TSL:1	n.722+6675G>A		intron	N/A
	ATP8B1	ENST00000857621.1		c.3532-15C>T		intron	N/A	ENSP00000527680.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30028 AN: 151812 Hom.: 3745 Cov.: 32

Gnomad AFR AF: 0.0655

Gnomad AMI AF: 0.0749

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.0161

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.228

GnomAD2 exomes AF: 0.217 AC: 32134 AN: 148126 AF XY: 0.221

Gnomad AFR exome AF: 0.0629

Gnomad AMR exome AF: 0.189

Gnomad ASJ exome AF: 0.279

Gnomad EAS exome AF: 0.00963

Gnomad FIN exome AF: 0.277

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.244

GnomAD4 exome AF: 0.253 AC: 353833 AN: 1396404 Hom.: 47070 Cov.: 33 AF XY: 0.252 AC XY: 173556 AN XY: 688616

African (AFR) AF: 0.0582 AC: 1834 AN: 31524

American (AMR) AF: 0.193 AC: 6900 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 6852 AN: 25150

East Asian (EAS) AF: 0.00787 AC: 281 AN: 35722

South Asian (SAS) AF: 0.208 AC: 16457 AN: 79254

European-Finnish (FIN) AF: 0.277 AC: 13569 AN: 48940

Middle Eastern (MID) AF: 0.235 AC: 958 AN: 4074

European-Non Finnish (NFE) AF: 0.272 AC: 293636 AN: 1078232

Other (OTH) AF: 0.231 AC: 13346 AN: 57812

GnomAD4 genome AF: 0.198 AC: 30032 AN: 151930 Hom.: 3745 Cov.: 32 AF XY: 0.196 AC XY: 14542 AN XY: 74252

African (AFR) AF: 0.0655 AC: 2715 AN: 41434

American (AMR) AF: 0.204 AC: 3112 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 939 AN: 3462

East Asian (EAS) AF: 0.0161 AC: 83 AN: 5146

South Asian (SAS) AF: 0.193 AC: 932 AN: 4822

European-Finnish (FIN) AF: 0.294 AC: 3112 AN: 10578

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18517 AN: 67906

Other (OTH) AF: 0.224 AC: 474 AN: 2112

Alfa AF: 0.244 Hom.: 19126

Bravo AF: 0.182

Asia WGS AF: 0.112 AC: 389 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	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	-0.83
CADD	Benign	3.9
DANN	Benign	0.41
PhyloP100		0.27
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: rs12958967; hg19: chr18-55315959;