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GeneBe

21-25764304-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_002040.4(GABPA):c.897G>A(p.Ala299=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,612,374 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0017 ( 6 hom. )

Consequence

GABPA
NM_002040.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.227
Variant links:
Genes affected
GABPA (HGNC:4071): (GA binding protein transcription factor subunit alpha) This gene encodes one of three GA-binding protein transcription factor subunits which functions as a DNA-binding subunit. Since this subunit shares identity with a subunit encoding the nuclear respiratory factor 2 gene, it is likely involved in activation of cytochrome oxidase expression and nuclear control of mitochondrial function. This subunit also shares identity with a subunit constituting the transcription factor E4TF1, responsible for expression of the adenovirus E4 gene. Because of its chromosomal localization and ability to form heterodimers with other polypeptides, this gene may play a role in the Down Syndrome phenotype. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Oct 2010]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 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=-0.43).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 21-25764304-G-A is Benign according to our data. Variant chr21-25764304-G-A is described in ClinVar as [Benign]. Clinvar id is 733491.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=-0.227 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 225 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GABPANM_002040.4 linkuse as main transcriptc.897G>A p.Ala299= synonymous_variant 8/10 ENST00000400075.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GABPAENST00000400075.4 linkuse as main transcriptc.897G>A p.Ala299= synonymous_variant 8/101 NM_002040.4 P1
GABPAENST00000354828.7 linkuse as main transcriptc.897G>A p.Ala299= synonymous_variant 8/101 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00148
AC:
225
AN:
152034
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00329
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00231
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00321
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00255
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.00158
AC:
395
AN:
250276
Hom.:
0
AF XY:
0.00159
AC XY:
215
AN XY:
135444
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000203
Gnomad ASJ exome
AF:
0.00179
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00421
Gnomad NFE exome
AF:
0.00242
Gnomad OTH exome
AF:
0.000822
GnomAD4 exome
AF:
0.00171
AC:
2495
AN:
1460222
Hom.:
6
Cov.:
32
AF XY:
0.00172
AC XY:
1250
AN XY:
726412
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00150
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00433
Gnomad4 NFE exome
AF:
0.00193
Gnomad4 OTH exome
AF:
0.00109
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00148
AC:
225
AN:
152152
Hom.:
0
Cov.:
32
AF XY:
0.00141
AC XY:
105
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.0000963
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00231
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00321
Gnomad4 NFE
AF:
0.00255
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.00212
Hom.:
1
Bravo
AF:
0.00125
EpiCase
AF:
0.00285
EpiControl
AF:
0.00237

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 20, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
Cadd
Benign
8.8
Dann
Benign
0.83

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: rs147015240; hg19: chr21-27136615; API