8-102239027-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The variant allele was found at a frequency of 0.0419 in 760,574 control chromosomes in the GnomAD database, including 3,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 522 hom., cov: 31)
Exomes 𝑓: 0.044 ( 2757 hom. )

Consequence

Unknown

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.308
Variant links:

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ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 8-102239027-C-A is Benign according to our data. Variant chr8-102239027-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 361183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-102239027-C-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt

Frequencies

GnomAD3 genomes
AF:
0.0333
AC:
5034
AN:
150976
Hom.:
513
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00486
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0819
Gnomad ASJ
AF:
0.0274
Gnomad EAS
AF:
0.383
Gnomad SAS
AF:
0.0874
Gnomad FIN
AF:
0.0290
Gnomad MID
AF:
0.00968
Gnomad NFE
AF:
0.0115
Gnomad OTH
AF:
0.0419
GnomAD4 exome
AF:
0.0439
AC:
26778
AN:
609486
Hom.:
2757
Cov.:
8
AF XY:
0.0447
AC XY:
14391
AN XY:
321844
show subpopulations
Gnomad4 AFR exome
AF:
0.00459
Gnomad4 AMR exome
AF:
0.104
Gnomad4 ASJ exome
AF:
0.0266
Gnomad4 EAS exome
AF:
0.357
Gnomad4 SAS exome
AF:
0.0768
Gnomad4 FIN exome
AF:
0.0296
Gnomad4 NFE exome
AF:
0.0113
Gnomad4 OTH exome
AF:
0.0461
GnomAD4 genome
AF:
0.0335
AC:
5058
AN:
151088
Hom.:
522
Cov.:
31
AF XY:
0.0375
AC XY:
2766
AN XY:
73788
show subpopulations
Gnomad4 AFR
AF:
0.00485
Gnomad4 AMR
AF:
0.0825
Gnomad4 ASJ
AF:
0.0274
Gnomad4 EAS
AF:
0.383
Gnomad4 SAS
AF:
0.0877
Gnomad4 FIN
AF:
0.0290
Gnomad4 NFE
AF:
0.0115
Gnomad4 OTH
AF:
0.0495
Alfa
AF:
0.0209
Hom.:
15
Bravo
AF:
0.0375

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Mitochondrial DNA depletion syndrome 8a Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxJun 16, 2018This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
6.4
DANN
Benign
0.81

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: rs2290707; hg19: chr8-103251255; COSMIC: COSV52567929; COSMIC: COSV52567929; API