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GeneBe

12-111679205-A-G

Variant summary

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

The NM_006768.5(BRAP):c.579T>C(p.Ile193=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,608,824 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 70 hom., cov: 30)
Exomes 𝑓: 0.0016 ( 51 hom. )

Consequence

BRAP
NM_006768.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.01
Variant links:
Genes affected
BRAP (HGNC:1099): (BRCA1 associated protein) The protein encoded by this gene was identified by its ability to bind to the nuclear localization signal of BRCA1 and other proteins. It is a cytoplasmic protein which may regulate nuclear targeting by retaining proteins with a nuclear localization signal in the cytoplasm. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-111679205-A-G is Benign according to our data. Variant chr12-111679205-A-G is described in ClinVar as [Benign]. Clinvar id is 768586.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=2.01 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BRAPNM_006768.5 linkuse as main transcriptc.579T>C p.Ile193= synonymous_variant 4/12 ENST00000419234.9
BRAPXM_005253944.5 linkuse as main transcriptc.702T>C p.Ile234= synonymous_variant 4/12
BRAPXM_017019992.2 linkuse as main transcriptc.417T>C p.Ile139= synonymous_variant 3/11
BRAPXM_047429622.1 linkuse as main transcriptc.132T>C p.Ile44= synonymous_variant 2/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BRAPENST00000419234.9 linkuse as main transcriptc.579T>C p.Ile193= synonymous_variant 4/121 NM_006768.5 P1Q7Z569-1
BRAPENST00000327551.6 linkuse as main transcriptc.489T>C p.Ile163= synonymous_variant 4/121

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0154
AC:
2342
AN:
152116
Hom.:
69
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0533
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00642
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.00861
GnomAD3 exomes
AF:
0.00408
AC:
1017
AN:
249532
Hom.:
32
AF XY:
0.00311
AC XY:
420
AN XY:
134910
show subpopulations
Gnomad AFR exome
AF:
0.0545
Gnomad AMR exome
AF:
0.00287
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000166
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000176
Gnomad OTH exome
AF:
0.00165
GnomAD4 exome
AF:
0.00160
AC:
2333
AN:
1456590
Hom.:
51
Cov.:
30
AF XY:
0.00135
AC XY:
979
AN XY:
724186
show subpopulations
Gnomad4 AFR exome
AF:
0.0535
Gnomad4 AMR exome
AF:
0.00295
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000141
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000110
Gnomad4 OTH exome
AF:
0.00427
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0155
AC:
2361
AN:
152234
Hom.:
70
Cov.:
30
AF XY:
0.0153
AC XY:
1139
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.0536
Gnomad4 AMR
AF:
0.00641
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.00947
Alfa
AF:
0.00850
Hom.:
10
Bravo
AF:
0.0169
Asia WGS
AF:
0.00693
AC:
24
AN:
3478

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 testingInvitaeMay 08, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
12
Dann
Benign
0.77
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs61308437; hg19: chr12-112117009; COSMIC: COSV100554058; API