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GeneBe

9-137018032-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001606.5(ABCA2):c.2037T>C(p.Asp679=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 1,612,726 control chromosomes in the GnomAD database, including 760,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.96 ( 70892 hom., cov: 33)
Exomes 𝑓: 0.97 ( 689854 hom. )

Consequence

ABCA2
NM_001606.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.603
Variant links:
Genes affected
ABCA2 (HGNC:32): (ATP binding cassette subfamily A member 2) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This protein is highly expressed in brain tissue and may play a role in macrophage lipid metabolism and neural development. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-137018032-A-G is Benign according to our data. Variant chr9-137018032-A-G is described in ClinVar as [Benign]. Clinvar id is 1185362.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.603 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABCA2NM_001606.5 linkuse as main transcriptc.2037T>C p.Asp679= synonymous_variant 15/49 ENST00000341511.11
ABCA2NM_212533.3 linkuse as main transcriptc.2127T>C p.Asp709= synonymous_variant 15/49
ABCA2NM_001411042.1 linkuse as main transcriptc.2034T>C p.Asp678= synonymous_variant 14/48
ABCA2XM_047422921.1 linkuse as main transcriptc.2124T>C p.Asp708= synonymous_variant 14/48

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABCA2ENST00000341511.11 linkuse as main transcriptc.2037T>C p.Asp679= synonymous_variant 15/495 NM_001606.5 P3Q9BZC7-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.965
AC:
146815
AN:
152192
Hom.:
70841
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.942
Gnomad AMI
AF:
0.986
Gnomad AMR
AF:
0.981
Gnomad ASJ
AF:
0.969
Gnomad EAS
AF:
0.997
Gnomad SAS
AF:
0.977
Gnomad FIN
AF:
0.966
Gnomad MID
AF:
0.959
Gnomad NFE
AF:
0.971
Gnomad OTH
AF:
0.967
GnomAD3 exomes
AF:
0.975
AC:
241477
AN:
247686
Hom.:
117747
AF XY:
0.975
AC XY:
131593
AN XY:
135016
show subpopulations
Gnomad AFR exome
AF:
0.942
Gnomad AMR exome
AF:
0.990
Gnomad ASJ exome
AF:
0.973
Gnomad EAS exome
AF:
0.996
Gnomad SAS exome
AF:
0.976
Gnomad FIN exome
AF:
0.971
Gnomad NFE exome
AF:
0.972
Gnomad OTH exome
AF:
0.975
GnomAD4 exome
AF:
0.972
AC:
1419411
AN:
1460416
Hom.:
689854
Cov.:
84
AF XY:
0.972
AC XY:
706070
AN XY:
726488
show subpopulations
Gnomad4 AFR exome
AF:
0.938
Gnomad4 AMR exome
AF:
0.989
Gnomad4 ASJ exome
AF:
0.974
Gnomad4 EAS exome
AF:
0.998
Gnomad4 SAS exome
AF:
0.977
Gnomad4 FIN exome
AF:
0.971
Gnomad4 NFE exome
AF:
0.971
Gnomad4 OTH exome
AF:
0.970
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.965
AC:
146927
AN:
152310
Hom.:
70892
Cov.:
33
AF XY:
0.965
AC XY:
71896
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.942
Gnomad4 AMR
AF:
0.981
Gnomad4 ASJ
AF:
0.969
Gnomad4 EAS
AF:
0.997
Gnomad4 SAS
AF:
0.977
Gnomad4 FIN
AF:
0.966
Gnomad4 NFE
AF:
0.971
Gnomad4 OTH
AF:
0.968
Alfa
AF:
0.971
Hom.:
108975
Bravo
AF:
0.965
Asia WGS
AF:
0.981
AC:
3411
AN:
3478
EpiCase
AF:
0.969
EpiControl
AF:
0.971

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Intellectual developmental disorder with poor growth and with or without seizures or ataxia Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 14, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.65
Cadd
Benign
3.1
Dann
Benign
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.

Other links and lift over

dbSNP: rs908832; hg19: chr9-139912484; COSMIC: COSV55804490; COSMIC: COSV55804490; API