18-79377202-A-G

Variant names:

• chr18-79377202-A-G
• rs1110784
• NM_198531.5:c.3308-45A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198531.5(ATP9B):​c.3308-45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 1,604,880 control chromosomes in the GnomAD database, including 616,818 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.89 (61057 hom., cov: 32)
  • Exomes 𝑓: 0.87 (555761 hom.)
• Consequence: ATP9B NM_198531.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 10 publications found

Genes affected

ATP9B (HGNC:13541): (ATPase phospholipid transporting 9B (putative)) Predicted to enable ATPase-coupled intramembrane lipid transporter activity. Predicted to be involved in endocytosis; phospholipid translocation; and retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum. Located in perinuclear region of cytoplasm and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP9B	NM_198531.5	c.3308-45A>G		intron_variant	Intron 29 of 29	ENST00000426216.6	NP_940933.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP9B	ENST00000426216.6	c.3308-45A>G		intron_variant	Intron 29 of 29	5	NM_198531.5	ENSP00000398076.2
ATP9B	ENST00000307671.12	c.3275-45A>G		intron_variant	Intron 28 of 28	1		ENSP00000304500.7
ATP9B	ENST00000588921.1	n.*195-45A>G		intron_variant	Intron 7 of 7	1		ENSP00000465269.1
ATP9B	ENST00000590477.5	n.*162-45A>G		intron_variant	Intron 7 of 7	2		ENSP00000467935.1

Frequencies

GnomAD3 genomes AF: 0.894 AC: 136036 AN: 152100 Hom.: 60997 Cov.: 32

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.898

GnomAD2 exomes AF: 0.900 AC: 220439 AN: 245010 AF XY: 0.901

Gnomad AFR exome AF: 0.928

Gnomad AMR exome AF: 0.918

Gnomad ASJ exome AF: 0.953

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.814

Gnomad NFE exome AF: 0.869

Gnomad OTH exome AF: 0.894

GnomAD4 exome AF: 0.874 AC: 1269325 AN: 1452662 Hom.: 555761 Cov.: 39 AF XY: 0.877 AC XY: 633725 AN XY: 722896

African (AFR) AF: 0.933 AC: 31219 AN: 33446

American (AMR) AF: 0.918 AC: 41035 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.949 AC: 24774 AN: 26098

East Asian (EAS) AF: 1.00 AC: 39675 AN: 39682

South Asian (SAS) AF: 0.947 AC: 81648 AN: 86220

European-Finnish (FIN) AF: 0.819 AC: 37523 AN: 45794

Middle Eastern (MID) AF: 0.942 AC: 5433 AN: 5766

European-Non Finnish (NFE) AF: 0.859 AC: 954599 AN: 1110666

Other (OTH) AF: 0.886 AC: 53419 AN: 60288

GnomAD4 genome AF: 0.894 AC: 136155 AN: 152218 Hom.: 61057 Cov.: 32 AF XY: 0.893 AC XY: 66481 AN XY: 74414

African (AFR) AF: 0.930 AC: 38637 AN: 41536

American (AMR) AF: 0.914 AC: 13986 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 3299 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5154 AN: 5158

South Asian (SAS) AF: 0.951 AC: 4584 AN: 4820

European-Finnish (FIN) AF: 0.808 AC: 8566 AN: 10598

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 59034 AN: 68008

Other (OTH) AF: 0.900 AC: 1904 AN: 2116

Alfa AF: 0.883 Hom.: 50479

Bravo AF: 0.903

Asia WGS AF: 0.964 AC: 3354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.47
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1110784; hg19: chr18-77137202; COSMIC: COSV56944959; COSMIC: COSV56944959;