Variant 9-98005025-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000339399.5(ANP32B):c.389A>C(p.Asp130Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,614,116 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 0.0013 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0010 ( 26 hom. )

Consequence

ANP32B
ENST00000339399.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 8.95

Variant links:

Genes affected

ANP32B (HGNC:16677): (acidic nuclear phosphoprotein 32 family member B) Enables RNA polymerase binding activity and histone binding activity. Involved in several processes, including activation of cysteine-type endopeptidase activity involved in apoptotic process; nucleosome assembly; and positive regulation of protein export from nucleus. Located in cytoplasm and nucleoplasm. Colocalizes with nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ANP32B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012089968).

BP6

Variant 9-98005025-A-C is Benign according to our data. Variant chr9-98005025-A-C is described in ClinVar as [Benign]. Clinvar id is 788592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00102 (1487/1461834) while in subpopulation AMR AF= 0.0323 (1445/44714). AF 95% confidence interval is 0.0309. There are 26 homozygotes in gnomad4_exome. There are 577 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 198 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANP32B	NM_006401.3 linkuse as main transcript	c.389A>C	p.Asp130Ala	missense_variant	4/7	ENST00000339399.5	NP_006392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANP32B	ENST00000339399.5 linkuse as main transcript	c.389A>C	p.Asp130Ala	missense_variant	4/7	1	NM_006401.3	ENSP00000345848	P1	Q92688-1
ANP32B	ENST00000473205.1 linkuse as main transcript	n.577A>C		non_coding_transcript_exon_variant	5/5	3
ANP32B	ENST00000486769.1 linkuse as main transcript	n.127A>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00130

AC:

198

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00482

AC:

1210

AN:

251240

Hom.:

AF XY:

0.00327

AC XY:

444

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0344

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00102

AC:

1487

AN:

1461834

Hom.:

Cov.:

AF XY:

0.000793

AC XY:

577

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0323

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.00130

AC:

198

AN:

152282

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.0119

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000221

Hom.:

Bravo

AF:

0.00266

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00374

AC:

454

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Pathogenic

0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-5.6

REVEL

Uncertain

0.54

Sift

Uncertain

0.014

Sift4G

Benign

0.063

Polyphen

0.40

Vest4

0.82

MVP

0.85

MPC

1.2

ClinPred

0.096

GERP RS

5.6

Varity_R

0.59

gMVP

0.45

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over