rs28997575
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1
The NM_000465.4(BARD1):βc.1075_1095delβ(p.Leu359_Pro365del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.023 in 1,614,032 control chromosomes in the GnomAD database, including 759 homozygotes. Variant has been reported in ClinVar as Likely benign (β β ). Synonymous variant affecting the same amino acid position (i.e. L359L) has been classified as Likely benign.
Frequency
Consequence
NM_000465.4 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BARD1 | NM_000465.4 | c.1075_1095del | p.Leu359_Pro365del | inframe_deletion | 4/11 | ENST00000260947.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BARD1 | ENST00000260947.9 | c.1075_1095del | p.Leu359_Pro365del | inframe_deletion | 4/11 | 1 | NM_000465.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0282 AC: 4294AN: 152090Hom.: 85 Cov.: 32
GnomAD3 exomes AF: 0.0289 AC: 7261AN: 251308Hom.: 169 AF XY: 0.0304 AC XY: 4124AN XY: 135812
GnomAD4 exome AF: 0.0224 AC: 32769AN: 1461824Hom.: 674 AF XY: 0.0238 AC XY: 17297AN XY: 727208
GnomAD4 genome ? AF: 0.0282 AC: 4294AN: 152208Hom.: 85 Cov.: 32 AF XY: 0.0284 AC XY: 2112AN XY: 74426
ClinVar
Submissions by phenotype
Familial cancer of breast Benign:7
Benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Feb 24, 2023 | This variant is considered benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. - |
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 27, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Jan 01, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Counsyl | Jul 06, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jul 08, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 19, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The BARD1 p.Leu359_Pro365del variant was identified in 19 of 926 proband chromosomes (frequency: 0.0205) from individuals or families with hereditary breast and ovarian cancer and was present in 4 of 140 control chromosomes (frequency: 0.03) from healthy individuals, and is reported in the literature as a polymorphism (De Brakeleer 2010, De Brakeleer 2015, Ishitobi 2003, Liu 2017, Irminger-Finger 2015). The variant was also identified in ClinVar as benign (by Ambry Genetics, GeneDx, Invitae, and Counsyl), and the Zhejiang Colon Cancer Database. The variant was not identified in Cosmic, and MutDB databases. The variant was identified in control databases in 7807 of 277012 chromosomes at a frequency of 0.03 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the following populations at a frequency greater than 1%: South Asian (52 homozygous) in 2152 of 30774 chromosomes (freq: 0.07), East Asian (8 homozygous) in 834 of 18854 chromosomes (freq: 0.044), African (9 homozygous) in 986 of 24026 chromosomes (freq: 0.041), Latino (2 homozygous) in 1167 of 34380 chromosomes (freq: 0.034), Other in 209 of 6462 chromosomes (freq: 0.032), European (Non-Finnish) in 2254 of 126574 chromosomes (freq: 0.018), Ashkenazi Jewish in 118 of 10152 chromosomes (freq: 0.012). This variant is an in-frame deletion resulting in the removal of a 7 amino acid residues from codon 359 to 365; the impact of this alteration on BARD1 protein function is not known. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:4
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 18, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 17, 2012 | - - |
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Oct 20, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 14, 2014 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 12, 2018 | - - |
Hereditary breast ovarian cancer syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | National Health Laboratory Service, Universitas Academic Hospital and University of the Free State | Apr 19, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at