chr7-135134832-C-A
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4BP6_ModerateBS1BS2
The NM_178563.4(AGBL3):c.2343-9C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,546,538 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 0.0070 ( 14 hom., cov: 32)
Exomes 𝑓: 0.00060 ( 13 hom. )
Consequence
AGBL3
NM_178563.4 splice_polypyrimidine_tract, intron
NM_178563.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.2887
2
Clinical Significance
Conservation
PhyloP100: 1.27
Genes affected
AGBL3 (HGNC:27981): (AGBL carboxypeptidase 3) Enables metallocarboxypeptidase activity. Involved in protein side chain deglutamylation. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
CYREN (HGNC:22432): (cell cycle regulator of NHEJ) Involved in double-strand break repair via nonhomologous end joining and negative regulation of double-strand break repair via nonhomologous end joining. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.16).
BP6
?
Variant 7-135134832-C-A is Benign according to our data. Variant chr7-135134832-C-A is described in ClinVar as [Benign]. Clinvar id is 788544.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.007 (1065/152184) while in subpopulation AFR AF= 0.0244 (1015/41544). AF 95% confidence interval is 0.0232. There are 14 homozygotes in gnomad4. There are 492 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 14 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGBL3 | NM_178563.4 | c.2343-9C>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000436302.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGBL3 | ENST00000436302.6 | c.2343-9C>A | splice_polypyrimidine_tract_variant, intron_variant | 2 | NM_178563.4 | P2 | |||
CYREN | ENST00000459937.5 | n.356+33917G>T | intron_variant, non_coding_transcript_variant | 1 | |||||
AGBL3 | ENST00000435976.6 | c.2111-12981C>A | intron_variant | 5 | A2 | ||||
CYREN | ENST00000464070.1 | n.187+13145G>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00701 AC: 1066AN: 152066Hom.: 14 Cov.: 32
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GnomAD3 exomes AF: 0.00138 AC: 208AN: 151104Hom.: 2 AF XY: 0.00101 AC XY: 81AN XY: 80296
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GnomAD4 exome AF: 0.000602 AC: 839AN: 1394354Hom.: 13 Cov.: 31 AF XY: 0.000492 AC XY: 338AN XY: 687240
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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 submitter | clinical testing | Invitae | Jun 11, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at