chr11-61950243-T-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001363592.1(BEST1):c.-221T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,722 control chromosomes in the GnomAD database, including 21,361 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.49 ( 21296 hom., cov: 32)
Exomes 𝑓: 0.44 ( 65 hom. )
Consequence
BEST1
NM_001363592.1 5_prime_UTR
NM_001363592.1 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.14
Genes affected
BEST1 (HGNC:12703): (bestrophin 1) This gene encodes a member of the bestrophin gene family. This small gene family is characterized by proteins with a highly conserved N-terminus with four to six transmembrane domains. Bestrophins may form chloride ion channels or may regulate voltage-gated L-type calcium-ion channels. Bestrophins are generally believed to form calcium-activated chloride-ion channels in epithelial cells but they have also been shown to be highly permeable to bicarbonate ion transport in retinal tissue. Mutations in this gene are responsible for juvenile-onset vitelliform macular dystrophy (VMD2), also known as Best macular dystrophy, in addition to adult-onset vitelliform macular dystrophy (AVMD) and other retinopathies. Alternative splicing results in multiple variants encoding distinct isoforms.[provided by RefSeq, Nov 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 11-61950243-T-C is Benign according to our data. Variant chr11-61950243-T-C is described in ClinVar as [Benign]. Clinvar id is 305113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BEST1 | NM_001363592.1 | c.-221T>C | 5_prime_UTR_variant | 1/10 | |||
BEST1 | XM_005274210.5 | c.-221T>C | 5_prime_UTR_variant | 1/10 | |||
BEST1 | XM_005274221.5 | c.-221T>C | 5_prime_UTR_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BEST1 | ENST00000534553.5 | c.-396T>C | 5_prime_UTR_variant | 1/5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.491 AC: 74628AN: 152032Hom.: 21260 Cov.: 32
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GnomAD4 exome AF: 0.435 AC: 249AN: 572Hom.: 65 Cov.: 0 AF XY: 0.433 AC XY: 148AN XY: 342
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GnomAD4 genome AF: 0.491 AC: 74717AN: 152150Hom.: 21296 Cov.: 32 AF XY: 0.503 AC XY: 37423AN XY: 74364
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Retinitis Pigmentosa, Recessive Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Autosomal dominant vitreoretinochoroidopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Vitelliform macular dystrophy 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at