Genetic Variant NM_198531.5:c.3308-45A>G (chr18-79377202-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Variant links:

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]

ATP9B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 link	c.3308-45A>G		intron_variant	Intron 29 of 29	ENST00000426216.6	NP_940933.3	O43861-1B3KSI8Q7Z3J4Q69YZ7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATP9B	ENST00000426216.6 link	c.3308-45A>G	intron_variant	Intron 29 of 29	5	NM_198531.5	ENSP00000398076.2	O43861-1
ATP9B	ENST00000307671.12 link	c.3275-45A>G	intron_variant	Intron 28 of 28	1		ENSP00000304500.7	O43861-2
ATP9B	ENST00000588921.1 link	n.*195-45A>G	intron_variant	Intron 7 of 7	1		ENSP00000465269.1	K7EJP9
ATP9B	ENST00000590477.5 link	n.*162-45A>G	intron_variant	Intron 7 of 7	2		ENSP00000467935.1	K7EQQ5

Frequencies

GnomAD3 genomes

AF:

0.894

AC:

136036

AN:

152100

Hom.:

60997

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.900

AC:

220439

AN:

245010

Hom.:

99537

AF XY:

0.901

AC XY:

120043

AN XY:

133266

show subpopulations

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 SAS exome

AF:

0.947

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.:

AF XY:

0.877

AC XY:

633725

AN XY:

722896

show subpopulations

Gnomad4 AFR exome

AF:

0.933

Gnomad4 AMR exome

AF:

0.918

Gnomad4 ASJ exome

AF:

0.949

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.947

Gnomad4 FIN exome

AF:

0.819

Gnomad4 NFE exome

AF:

0.859

Gnomad4 OTH exome

AF:

0.886

GnomAD4 genome

AF:

0.894

AC:

136155

AN:

152218

Hom.:

61057

Cov.:

AF XY:

0.893

AC XY:

66481

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.930

Gnomad4 AMR

AF:

0.914

Gnomad4 ASJ

AF:

0.950

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.951

Gnomad4 FIN

AF:

0.808

Gnomad4 NFE

AF:

0.868

Gnomad4 OTH

AF:

0.900

Alfa

AF:

0.882

Hom.:

42617

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over